The swinging-bachelor lifestyle of commercial-jingle composer -- and chronic gambler -- Charlie Harper (Sheen) was sorely disrupted when his Malibu beach house was invaded by his uptight brother, Alan (Cryer), and Alan's ten-year-old son, Jake (Jones). Given the childish hedonism of Charlie and the domestic immaturity of the soon-to-be-divorced Alan, young Jake turned out to be the true "grown-up" in the Harper household.
Out for coffee with Alan and Jake, Charlie bumps in to a woman he had dated about nine years prior, and before going up to her, he notices an 8-year-old boy with her. The boy looks exactly like Charlie and Alan immediately picks up on this. Charlie is in denial that he could have a son, and Alan tries to convince him of the uncanny resemblance. Charlie finally gives in and attempts to do the right thing. In the long run we learn that this woman is conning Charlie, but he never finds out.
On his way out for the night Charlie realizes he's out of tip money and asks Alan how much cash he has on him. Alan has $38 which Charlie basically begs to borrow. Ever the tightwad, Alan wakes Charlie up early the next morning to get his money back, but Charlie still doesn't have any cash on him. Shocked by Alan's stingy attittude, Charlie decides to have fun with it by paying Berta back $100 for a pizza right in front of Alan, but still refusing to pay him back. This drives Alan nuts and he decides to siphon gas out of Charlie's car. An argument ensues and Alan tells Charlie he's moving out. While dropping Jake off at Judith's house, Herb (Ryan Stiles) tells Alan he can stay with them. Wanting Alan out of her house, Judith finds a way to get Charlie and Alan to reconcile. Meanwhile, Evelyn gives Jake a part time job as a sign twirler for a new condo development. Jake is horrible at it and ends up being replaced by a monkey.
Alan starts dating two women at the same time, and things initially work out without a hitch. Alan dismisses Charlie’s advice that things could get complicated, and that he should have lies ready just in case they start to suspect he’s two timing them. Naturally, Alan is put in the hot seat when he is asked directly by one of the women if he is seeing other people. He stammers for a moment and admits that yes, he is, and she kicks him out. After getting the boot from his first girlfriend, he heads over to the second’s house to surprise her. Once there he discovers that she too is seeing other people, and he ends up losing both of his girlfriends in the same night. Meanwhile, Jake has his first experience with alcohol, and Charlie is forced to help him deal with the effects of drinking too much.
Alan turns to Charlie for a ride to work when his car is in the shop, leading Charlie to meet Alan's attractive receptionist. Charlie pursues the young woman, Melissa, and much to Alan's chagrin she agrees to have drinks with Charlie at the house. Alan insists to Charlie that he back off, as this is the best assistant he's ever had and he doesn't want to complicate things. However, Charlie insists that he's a changed man looking for an honest relationship, and all Alan can do is watch and wait. Of course, after spending a whole weekend together Charlie decides he and Melissa need to slow things down. This destroys Melissa, who takes out her anger on Alan, demanding additional benefits for the work she does for him.
Alan and Charlie bump in to Desiree Pasternak, Jake’s 5th grade teacher, who Charlie had seduced years before. After Charlie dumped her she went off the deep end, losing not only her sanity, but her job, family and self worth, eventually ending up as a stripper living in a run down hotel. Feeling guilty about destroying this young woman’s life, Charlie offers her a good job tutoring Jake. Things work out great at first, until Charlie discovers Desiree is a Jesus freak, who makes them all attend church. Not able to sustain his act of good will, Charlie bails on Desiree, Alan and Jake during the service. Realizing she’d been dumped again by Charlie, Desiree snaps and the church sends her away to a spiritual retreat.
After Judith asks Alan to take care Jake for three straight months, Alan and Charlie discover it’s because she and Herb are having marital problems. Later, Herb comes over to drop some things off for Jake and Charlie offers him some bad advice on how to deal with Judith. Herb does as Charlie suggests and Judith kicks him out. He then tries to get Charlie to hang out with him, and after Charlie repeatedly ignores his calls, he tracks him down at Pavlov’s. Meanwhile, Alan is thrilled by the problems Herb and Judith are going through, as they prove he wasn’t the only one to blame in the destruction of their marriage. He goes over to Judith’s to gloat about it but ends up sleeping with her as she informs him that she is never, ever going to let him go, freaking him out about what’s to come.
After sleeping with Judith when she and Herb separated, Alan decides he can't rush in to anything serious with her again and meets her for dinner to make that clear. However, desperate not to end up an old maid, Judith seduce Alan and they end up hooking up again. Meanwhile, Herb tries to make the best of his separation from Judith and continues hanging around with Charlie. Their night out leads them back to Herb’s sad bachelor pad with a couple of prostitutes, which ends up being too much to handle for Herb, who can’t get over Judith. Herb shows up at Judith’s while she and Alan are getting intimate and yells through the door that he still loves her. Hearing this, Judith tells Alan to leave through the back door, as she still loves him. Things return to normal until six weeks later, when Judith announces that she is pregnant.
After dating for about a month, Charlie’s new girlfriend, Chelsea, asks him to spend a night at her house and Charlie begrudgingly agrees. A creature of his ways, Charlie tries his best to settle in for the night, but can’t get over the many things that remind him that he is totally out of his element and he leaves in the middle of the night. Unwilling to let Chelsea go without a fight, Charlie tries to spend the night again the next night. However, this time he comes prepared with all of the comforts of his own home which leaves Chelsea less than thrilled. Meanwhile, Jake deals with being grounded from all electronic media after mooning the girls track team from his school bus.
After hearing that Alan has to go to Beverly Hills to check on Evelyn’s house, Charlie enlists Alan to take his Mercedes to the dealership, which is in the same part of town. Once there, Alan ends up meeting an attractive woman, Diane, and takes her to lunch. After lunch they end up back at Evelyn’s, which Alan says is his own house, and Alan makes his move. All is going well until they stumble in to Evelyn’s bedroom, where they find a dress lying on the bed, leading Diane to think that Alan is married. Alan claims that the dress is actually his and that he likes to play dress up, and he tries to prove it by putting it on in the bathroom. Meanwhile, Diane rifles through Alan’s pockets and steals Charlie’s Mercedes. Back in Malibu, Charlie helps introduce Jake to his new neighbor’s daughter, only to have Jake disappear with her all day. This wouldn’t normally be a problem, but Charlie’s new neighbor is an overprotective ex-football star known as Jerome “Mad Dog” Burnett.
Evelyn invites Charlie, Alan and Jake over for dinner to announce that she has set aside enough money to pay for Jake’s college education, and as motivation, enough to buy him a car as well. Shocked by her generosity, Charlie and Alan try and discover what kind of ulterior motive Evelyn had to do such a thing. Alan is more thrilled than anything else by this development and knowing that his main financial obligation has been relieved, he begins to slack off at work. Unfortunately, a sedentary lifestyle is unfulfilling to Alan, who comes to the revelation that Evelyn’s ulterior motive was to squash his ambitions for her own amusement. Meanwhile, Jake is much more interested in what kind of a car he will be getting, and while trying to show off his cooking skills he inadvertently burns Evelyn’s kitchen down.
When Charlie’s good friend Andy dies prematurely, Charlie feels that his time on earth may be drawing to a close as well. Not only does he rush off to the doctor to get a complete check out, he also buys gifts for his friends and family (naturally excluding Alan) to ensure that he is remembered fondly if his life has run its course. He becomes so desperate to create a legacy for himself that he prepares to propose to Rose, but just as he is about to he gets word that he is 100% healthy and he returns to his hedonistic ways.
When Alan and his assistant, Melissa, share a few kisses at his office Alan puts a stop to it right away, insisting that they keep things professional. Once back at home Alan can’t stop obsessing over Melissa, so he throws caution to the wind and surprises Melissa at her house. However, once there he finds that her live-in, pot smoking mother makes hooking up with her next to impossible. Meanwhile, when Jake and Charlie are invited over to dinner at a hot twenty-something’s house they end up battling it out for her affection.
Alan has completely convinced himself that it was he, and not Herb, who conceived a child with Judith, and when he finds out that they have begun renovating a room for their expected baby daughter, he becomes obsessed with helping. While working with Herb, Alan can’t help but inject his own opinions and feelings into how they should raise the baby, until Judith catches on to what he’s doing and gives him the boot. Meanwhile, Charlie helps Jake figure out how to deal with an “experienced” girl who has a crush on him.
Alan’s girlfriend, Melissa, throws him a surprise 40th birthday party which goes horribly. During the party Berta, Charlie, Evelyn and Jake ridicule and belittle Alan so incessantly that Melissa insists that he come and live with her and her pot addled mother. Thrilled to be living in a loving and caring environment, Alan is just starting to get comfortable when he unknowingly samples some of Melissa’s mother’s pot laced banana bread. Melissa then walks in on her mother and Alan in a compromising and embarrassing position. Meanwhile, Charlie is surprised to find that he actually misses Alan, and Jake barely notices he’s gone.
Charlie and Chelsea are still dating but have fallen in to a bit of a rut, prompting Chelsea to end the relationship after one too many nights staying in, watching TV and eating Chinese take out. Charlie is hurt badly by the break up, but with no idea how to compensate for it he begins overindulging in sweets and pudding. Charlie seeks out Dr. Freeman for guidance, and ends up taking Chelsea with him to couple’s counseling session in order to get her back. However, after attending the appointment he realizes couples therapy might not be the best solution. Meanwhile, Alan takes pleasure in watching Charlie suffer through couples counseling, and Jake tries in vain to keep some pudding in the house.
Charlie’s girlfriend Chelsea has to go away to her Ex-Mother-in-law’s funeral, and Charlie begins to experience some jealousy when he discovers she will be staying with her ex-husband. The night Chelsea is gone Charlie gets a surprise visit from a drunk and horny former fling, Wanda, and still feeling jealous he takes her to bed. However, once there he finds that he loves Chelsea too much to cheat on her. Just then, Charlie gets a call from Chelsea, who tells him she’s cut her trip short, and that she’ll be over soon. Charlie is then forced to enlist Alan and Jake’s help getting the drunk and half naked Wanda out of the house before Chelsea gets there.
When Charlie tells Chelsea that he loves her, she replies with a simple "thank you." Not used to putting his feelings out there and not having them be reciprocated, Charlie goes to Dr. Freeman to talk the issue through. He finds that he needs the relationship to be on equal terms, and in order to get Chelsea to say "I love you," he decides to ask her to marry him. However, when he tries the old "engagement ring in a glass of Champagne" routine, Chelsea accidentally swallows the ring.
When Charlie’s girlfriend Chelsea comes down with the flu, his natural reaction is to send her home so he can avoid getting sick. However, trying to prove how much he loves her, Charlie asks Chelsea to stay over so he can take care of her. Charlie then suffers through all of the humiliating tasks involved with helping Chelsea get better, and eventually he ends up sick himself. Meanwhile, Alan tries to be supportive of Charlie and Jake deals with a nine year old that has a crush on him.
When Chelsea discovers some topless photos of an ex-girlfriend on Charlie’s cell phone, she storms off after breaking up with him. Meanwhile, Herb and Alan are both dealing with relationship problems as well, and all three men find themselves hanging out at Charlie’s, commiserating over their shared frustration with women. Charlie’s neighbor Jerome (Ep. 609), who’s daughter is out on a date with Jake, joins in as well and all the men end up drunk. Ultimately, Charlie can’t face a future where he just hangs around with the guys complaining, so he sets his sights on getting Chelsea back.
Chelsea and Evelyn meet for the first time, and Chelsea discovers that Charlie hasn’t told Evelyn about their engagement. In order to make this up to her, Chelsea starts spending time with Evelyn and the two become friends. Sure that his mother has ulterior motives, Charlie tries to get Chelsea to understand what a wicked person Evelyn is, but Chelsea doesn’t believe him. He then asks Alan and Jake to back up his story, only to discover that Evelyn has bought them off. Ultimately, Charlie tracks down Chelsea’s equally crazy mother and has her come out to California, and Chelsea agrees to stop spending time with Evelyn in order to get rid of her.
When Alan becomes a little too obsessed with building model cars, Chelsea insists that she and Charlie set him up with one of her girlfriends. She sets up a double date, and when Charlie and Alan show up at the restaurant they discover Chelsea’s friend is Rose, who had befriended Chelsea to keep an eye on Charlie. Not wanting to scare her off, Rose hadn’t said a word about her history with Charlie to Chelsea, and to avoid rocking the boat, Charlie and Alan keep quiet as well. However, as the date progresses Alan and Rose really start to hit it off and they end up spending the night together. Alan realizes the mistake he’s made when Rose begins stocking him, and when he suggests they set boundaries Rose gets him where it hurts most.
Chelsea and Charlie get into a huge fight after the lease on her apartment ends and she suggests she move in to his place, even though he still wants his own space. After some soul searching and a chat with Alan, Charlie realizes he was wrong and asks Chelsea to move in with him. However, when she gets there she changes things all around, from the shower curtains to the salt and pepper shakers, which freaks Charlie out even more and another fight ensues. Alan then helps Charlie smooth things over with Chelsea again, only to discover that now that she's moved in, they are using his room as a storage closet. Ultimately, Charlie solves the problem by secretly renting Chelsea’s old apartment for himself.
Charlie and Chelsea are on their way out for the night and Chelsea notices that Alan has sunken to an all time low, he’s brought out his ventriloquist doll. She invites Alan along and Charlie hesitantly agrees to let Alan tag along. Alan and Chelsea hit it off and Charlie realizes that he can have the best of both worlds. Alan is the perfect girlfriend for Chelsea as we see them going to the museum, watching a chick flick and going shopping. Between Charlie and Alan we have the perfect guy. Alan does all the girl stuff with Chelsea while Charlie gets to reap the benefits in bed. Things seem to go great up until Alan begins to feel used which throws the whole relationship between the three of them in an uproar. In the end Alan retreats back to his ventriloquist doll.
Charlie starts to question his relationship with Chelsea when he hears that Mia is back in town. Meanwhile, Judith goes into labor and Charlie, Alan and Herb rush her to the hospital, on the sixth season finale.