House is secretly trying to treat a fighter pilot who is a candidate for NASA's astronaut training program. Her diagnosis will be the test to choose which ones of the 40 applicants are going to take the empty spots in his team.

The candidates are now two teams of five women and five men, competing on diagnosing and treating a wheelchair-bound man. Meanwhile House does experiments on himself to test what happens after death, and Foreman, at another hospital, is treating his team in a House-like manner.

House finds that some of his own fellowship students will do whatever it takes, when they deal with a woman who believes she can talk to the dead.

House deals with a patient who mirrors the personality of anyone he meets. Meanwhile, Foreman is put in charge of overseeing the fellowship candidates.

Based on practically no information and no medical history about a mystery patient sent by the CIA, House is using some unorthodox methods to diagnose and treat him. Meanwhile the remaining candidates are questioning Foreman's judgment.

A film crew and the candidates are following around House distracting him while he is trying to diagnose a teenager who suffers from a heart attack prior to a serious plastic surgery.

House treats a magician but comes to believe he's faking illness to cover up his own incompetence. Meanwhile, House pits the fellows against each other in his version of an immunity challenge.

Under Cuddy’s pressure to choose his team, House gives the candidates a case of a former punk rock star who is a drug user. Whoever diagnoses the patient is going to have a future as a member of House’s team.

House and his team have to diagnose a case at a distance when a researcher at a South Pole base is taken ill.

House and his team must diagnose a Jewish bride who is taken ill at her wedding. However, House is more interested in analyzing Wilson's relationship with his new girlfriend.

House copes with a patient whose symptoms conceal a greater problem, but spends much of his time dodging Cuddy's orders to give performance reviews, and fighting with Amber over who gets to spend more time with Wilson.

House is convinced one of the actors on his favorite soap opera “Prescription Passion” has a serious medical condition after observing his symptoms on television. House decides to intervene and take matters into his own hands, but both the actor and House's own team dismiss House’s assessment and do not believe there is anything wrong with him.

A bus accident leaves House with serious head trauma and partial amnesia. He comes to believe that a patient on the bus had a life-threatening disease and struggles to recall who it was, and what they had.

In the aftermath of the bus accident, House struggles with his head injuries and short-term memory loss, and must deal with a concerned Wilson who believes his friend's health may be in danger.

Cameron postpones her vacation with Chase in order to ask House to accept the case of an environmental radical who collapsed at a protest with unexplainable symptoms. Although suspicious of her motives, House agrees. Since she pushed him to take the case so emphatically, House forces Cameron to take the lead and run many of the tests on the patient. Meanwhile, House is unsure of Wilson’s new healthy diet.

The team takes on the case of a deaf 14-year-old named Seth who collapsed after he started “hearing” explosions while competing in a wrestling match. When the team tries to test him for seizures, Seth loses vision in one eye, complicating House’s bunk theory of “Exploding Head Syndrome.” As his condition worsens, the team has an ethical disagreement about the patient and his mother’s adamant decision to forego cochlear implants to supplement his hearing. When the prospect of giving Seth the ability to hear for the first time in his life arises, House and the team are faced with a resounding decision. Meanwhile, House’s lack of sleep starts to play tricks on his mind, but he finds his insomnia may be a gift instead of a burden

House and the team take on the case of a ballerina whose lungs collapse in the middle of a performance. When the treatment causes her skin to fall off, the dancer faces not only the prospect of never dancing again but also of dying an agonizing death. The team must use their imaginations to carefully choreograph ways to test and treat her delicate body without killing her. Meanwhile, House continues to suffer from what he thinks is insomnia, and he is willing to go to desperate measures to cure it.

House and the team are intrigued by Scott, a man whose left brain and right brain operate independently, leaving him with two distinct personalities and no control over some of his actions. As the two sides of Scott’s brain struggle for dominance, his warring personalities make it increasingly difficult for the team to figure out what is causing the unique problem. The team is forced to use some unusual methods to get him to cooperate with their necessary testing. Meanwhile, when House refuses to make an appearance in the clinic, Cuddy takes an unconventional approach to force House to make up the time with a particular patient.

Facing a 6-month jail term, and the realization that he won't be there for Wilson at the end, House finds himself examining his entire life while contemplating a dismal future without his best friend.