Leonard and Sheldon are brilliant physicists. But none of that genius helps them interact with people, especially women. All this begins to change when a free-spirited beauty named Penny moves in next door.
Brilliant physicist roommates Leonard and Sheldon meet their new neighbor Penny, who begins showing them that as much as they know about science, they know little about actual living.
Sheldon and Leonard go over to Penny's apartment to drop off a package that came for her. Sheldon is deeply disturbed when he sees how messy and disorganized her apartment appears. Later that night, when Leonard is sleeping, Sheldon sneaks into Penny's apartment to clean and organize it. Leonard catches him and tries to stop him, but Sheldon is obsessed. When Penny wakes to find what Sheldon has done she is furious.
When Leonard sees Penny kissing a guy in front of her apartment door he is devastated. The guys convince him to ask someone out at work, but when he tries and is brutally turned down by a geeky girl, he is even more depressed. Wolowitz conspires to take them all to salsa class at the community center, where he meets all of his conquests. The women there are all 85 and up or 6 feet tall. Leonard finally decides to ask Penny out to dinner and just when he thinks he is making progress, she tells him that it is too soon for her to start dating again.
Sheldon is fired from his job as a physicist at the university when he blows up at his boss who he thinks is not a smart as he is. His change of circumstance sends him into a downward spiral of depression which the boys try to cure by sending for Sheldon's mom. When his mom arrives for a visit, the boys realize his mom is completely the opposite of what they expected. They would never have guessed Sheldon was related to her as she is simple and sweet. But the visit works, and Mom is able to successfully get Sheldon back on track.
While eating at the restaurant where Penny works, Leonard and Sheldon run into Leslie, a fellow scientist who works with Leonard.
The guys go to Penny's Halloween party. Leonard ends up getting humiliated by Penny's hunky ex-boyfriend while Sheldon, Wolowitz and Koothrappali try desperately to make a mark on the social scene but with limited success. After the party, Penny is a little drunk and sad after seeing her ex and ends up kissing Leonard.
Penny's promiscuous friend comes to town and Wolowitz hooks up with her. This leaves the guys without their fourth wheel. Sheldon goes a little crazy because his world has been thrown off, and Penny has to stay with the guys in their apartment. With Wolowitz preoccupied, the guys discover they are without a fourth member of their group, and in desperation, they ask Penny to join their Halo team.
Koothrappali is overwhelmed after his parents arrange a blind date, but he discovers he actually can talk to the opposite sex after a few drinks; however, complications set in when his beautiful date is more interested in Sheldon. Penny has started her new job as a bartender so Koothrappali decides to have the date at her restaurant, but he blows it and Sheldon ends up getting the girl.
When Sheldon and Leonard are invited to present their joint findings at a physics conference, Sheldon refuses. But when Penny steps in to mediate, it only deepens the rift between the two best friends.
The guys are invited by Penny to see her in a performance of Rent, but they know how horribly she sings, so Leonard lies to get out of it. But Sheldon is so disturbed by the lie, that he makes up a very intricate new lie, which he thinks is better. They tell Penny that Sheldon has a cousin who is a drug addict, and they have to do an intervention in Long Beach. They invite over a fellow physicist, who minored in theater in college -- to be the cousin. Penny comes over, and falls for the whole thing.
When Sheldon comes down with the flu, all the guys escape knowing what he is like when he is sick. Sheldon then turns up at Penny's restaurant asking for soup. She ends up leaving work, and taking care of him.
In this episode a 14 year old wunderkind is introduced to the physics lab where Sheldon and Leonard work. Sheldon is threatened by this boy, because he can take Leonard's title of youngest genius away. Sheldon suffers a crisis of confidence, and his friends try to console him. In an attempt to restore his sense of purpose, the boys come up with a solution to derail the newcomer's research.
The guys engage in the University Physics bowl. But Sheldon is so obnoxious, he is kicked off the team. So he forms his own team with the janitor and the cafeteria lady, and he goes up against his buddies. Leslie Winkel played by Sara Gilbert returns in this one to join Leonard's team and kick Sheldon's butt.
When the guys buy the old time machine prop from the movie, Penny accuses them of acting like children and tells them to grow up. This prompts Leonard to get rid of all of his nerdmorabilia, as he realizes that girls like Penny don’t end up with guys who have time machines. But when Leonard sees Penny on a date with a gorgeous hunk, he decides to keep his things.
Sheldon's twin sister comes into town, and she is a complete knockout. Leonard, Wolowitz, and Koothrappali go crazy for her and compete for her attention. When Leonard devises a plan to eliminate his rivals, it backfires when Sheldon declares he will decide whom his sister dates.
The gang finds out that Leonard's birthday is coming up. Penny wants to throw him a party, but she finds out that his family never celebrated his birthdays. Penny decides to throw him a surprise party and enlists Sheldon to help her out. Wolowitz participates by taking Leonard to the emergency room with him, under the pretense that he ate a peanut and is having a massive allergic reaction. By the time they make it back the apartment, the party is over. Penny feels terrible and gives Leonard a big kiss.
Penny finally breaks up with her boyfriend, giving Leonard the courage he needs to ask her out on a real date. She agrees to the date. However, before they actually go out, they both seek the “wisdom” of reluctant advisor, Sheldon, on separate occasions. The Tangerine Factor is the first season finale of “The Big Bang Theory.”