In the Season Four finale, a massive bus accident left House without recollection of four hours prior to the accident. The team helped House discover Wilson's girlfriend Amber was on the bus with him and was fatally injured. Wilson had to face the shocking realization that House was directly involved in Amber's death. As Season Five opens, with his friendship with Wilson shattered, House must determine if he's responsible for Amber's death and Wilson must decide if House is a destructive force in his life, while Cuddy attempts to advance a reconciliation between the two.
In the middle of a meeting, a woman named Lou is tending to her boss when she swats at what she thinks is an ant crawling on her arm. She then feels another ant on her neck. Lou rips her shirt open, and starts clawing at her bare chest in an absolute panic as she thinks hundreds of ants cover her.
A tennis player, a construction worker, a mixed martial artist and a tuba player each suddenly collapse and die. Thirteen goes to the classroom of Apple Weiss who is at the blackboard teaching college mathematics. All the patients who received a transplant five years ago are either dead or dying. Apple is on that list after receiving a corneal transplant. She is sent to the ICU of Princeton-Plainsboro while an older man named Frank lies nearby in an open bed, dying.
Artist Brandon Haggerty is focused intently on his easel as he sketches a woman in the nude while her husband watches. Yet when the couple finally gets to see the painting, they are horrified. Brandon doesn't understand their reaction and the husband punches him. Brandon's girlfriend Heather realizes that the painting is an ugly, distorted caricature.
A young Chinese-American woman named Nicole searches for her birth parents in a Buddhist temple in China. She spots a couple that she believes is her parents and has an interpreter named Fang speak to them. They reject her. Nicole goes to the Buddha that the couple had been praying at and lifts it from its stand. Fang says that, if she cannot lift the Buddha again, her wish will be granted. Nicole bows her head for a moment then tries to pick it up. She struggles, falls to one knee and begins to vomit blood.
Thirteen brings her one-night stand to the hospital after the woman has a seizure. However, the woman admits she slept with Thirteen just so she could get to House and have him diagnose her condition. Meanwhile, House continues to pay Lucas to spy on Wilson.
A man named Jerry gets to work in his kitchen sampling coffee from a series of coffeemakers. He is a consumer product tester. His daughter Samantha leaves for school. Suddenly, he realizes that all the coffeemakers have disappeared. Samantha comes back into the house and he thinks she has forgotten something. She says that it is many hours later and she has returned home from school. Jerry is confused. He has experienced a lapse in time.
An agoraphobic man (guest star Todd Louiso) falls mysteriously ill and adamantly refuses to leave his home, forcing House (Hugh Laurie) and the team to go to him for treatment. Meanwhile, Cameron (Jennifer Morrison) and Chase (Jesse Spencer) attempt to work through kinks in their relationship, House deals with an annoying itch he cannot seem to scratch and Wilson (Robert Sean Leonard) has his own ideas about House’s prickly situation.
The team tackles the case of a 16-year-old factory manager and emancipated minor (guest star Emily Rios) who falls ill at work, while Foreman (Omar Epps) takes on his own pediatric case. But when the child’s (guest star Kyle Silverstein) unexplained illness brings him to the brink of death, Foreman is left questioning his ability to work without House’s oversight.
A man (guest star Ivanek) willing to kill – or die – for a diagnosis takes House, Thirteen (Olivia Wilde) and several patients from the hospital waiting room hostage in Cuddy’s office. With one person shot, other patients needing medical attention, Thirteen being used as a guinea pig and the SWAT team closing in, House is determined to end the standoff the only way he knows how: by coming up with the right diagnosis.
The team take on the case of a fitness guru on an all-natural diet who collapsed while filming a video. Meanwhile, Foreman conducts Huntington's Disease drug trials and Thirteen signs on as a subject, Cuddy is forced to move into House's office, and Kutner uses House's name to run an online medical-advice website.
House and his team deal with a bullied girl who collapses during her school's Christmas program. Meanwhile, Foreman and Thirteen grow closer during the Huntington's disease drug trials, House gives a patient a gift, the staff wonder who gave House a special gift, and Cuddy gets an unexpected gift.
A man named Jeff solemnly writes a letter and signs it with, "I'm sorry." He removes his wedding ring and takes out shirts from the closet. His wife and son arrive at the house to find the shirts piled in a line across the front of the garage. Jeff is passed out in the car with the motor running. His wife frantically pulls him from the car.
Cuddy decides to spend more time at home to take care of her newly adopted baby and passes some of her day-to-day responsibilities off to Cameron.
House and the team take on the case of a woman who collapsed in the middle of a cooking class, and they soon learn she is a highly-renowned cancer researcher.
A young priest named Daniel Bresson retreats to his tiny apartment upstairs from the homeless outreach center that he has just closed for the night. While drinking a glass of scotch, he hears a knock on the door downstairs. Annoyed, he opens the door to see a Jesus-like figure standing there, hovering above the ground.
A patient with both male and female DNA has the team stumped. Meanwhile, House starts acting nicely, raising Cuddy's and Wilson's suspicions that something is terribly wrong.
House and the team take on the case of Nick, a book editor who loses his inhibitions. The team realizes Nick has frontal lobe disinhibition, which causes him to speak his mind having no control over what he says and making him just like House. Meanwhile, House suspects Wilson and Taub are keeping something from him.
A nursing home worker, Morgan, fakes an illness to get House to examine a cat which can predict the death of elderly patients. House doesn't believe it... until Morgan becomes ill for real.
House is in the ER of Middletown General Hospital after crashing his motorcycle.
The team deals with an older woman who has been tending to her dying husband but is stricken down with an unknown disease that threatens to kill her before her husband. However, they must overcome their own emotions when a tragedy strikes one of their members.
A group of protestors sit with their arms chained outside a coal mine. Angry employees try to stop them. A protester named Doug speaks up and a rock is thrown at his head, barely missing him.
At a high school wrestling competition, player Seth Miller is deaf. As he grapples for control in the middle of his match, he hears what sounds like an explosion followed by another. Seth collapses onto the mat.
At Lincoln Center, two ballet dancers, Penelope and Jeremy, rehearse. Jeremy fails to catch Penelope as she leaps, causing her to crash on the floor. She is unable to breathe and her lungs struggle.
An obnoxious patron at a restaurant gets hit by dinner rolls each time he complains. Dining next to him is a couple named Scott and Annie. Scott pushes their basket of rolls away and holds down his left wrist. The patron assumes it was Scott who threw the rolls at him, so he confronts him. Scott apologizes, but his left hand pours a glass of water on the guy's pants. As the man grabs Scott, a tear of blood runs from Scott's eye and down his cheek.