In the Season Three finale, the set-in-his-ways House was confronted with a series of major changes to his team - neurologist Dr. Eric Foreman (Omar Epps) left Princeton Plainsboro because he didn't want to turn into House; House randomly fired old-money intensivist Dr. Robert Chase (Jesse Spencer); and immunologist Dr. Allison Cameron (Jennifer Morrison) resigned, knowing House will be completely unaffected by her decision. But any effects of this "house-cleaning" on House, or the changes it may bring professionally or personally, remain to be seen...
With his diagnostic team gone, House tries to diagnose a young woman who survived an office building collapse. With the condition getting worse, Cuddy puts pressure on House to hire a new team, but instead attempts a differential diagnosis with help from the janitor.
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.
A mother's sudden paralysis during a indoor rock-climbing incident leaves her daughter injured, and House's new team looking for a cure. Meanwhile, House organizes his new recruits' Secret Santa gift exchange... with a few twists of his own.
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 the team encounter a woman (guest star Laura Silverman) admitted to Princeton-Plainsboro after she collapsed at her wedding. Her test results come up negative for a variety of common diseases, which leads the team to suspect foul play. When they discover the woman had been a music producer living in the fast lane until she began to practice Hasidic Judaism, House insists that people do not change, and that her seemingly rash decision may be a symptom of the underlying condition.
House suspects an emergency room patient has a bigger problem than the E.R. initially diagnosed based on the fact that the patient is too nice. A skeptical House questions the patient's sunny disposition as the team tries to get to the bottom of his illness, but disagrees with House that niceness is a symptom. Meanwhile, House and Amber are at odds about how much time they each get to spend with Wilson, and Cuddy demands House give his team performance reviews.
House is convinced one of the actors on his favorite soap opera (guest star Jason Lewis) “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. Meanwhile, Amber and Wilson have their first argument, and Cuddy tries to keep up appearances when an inspector makes an unexpected visit to Princeton-Plainsboro.
House finds himself dazed, confused and covered in blood after surviving a bus accident that left dozens seriously injured. Unable to clearly recall the events leading up to the crash due to his head injuries, House becomes convinced through his flashbacks that a fellow bus passenger was exhibiting signs of a deadly illness prior to the crash. Much to the team's dismay, House pushes through the pain of his own injuries, desperate to piece together the fragments of his shattered memory in order to save someone who might not even know he or she could be dying.
Clues inside House's head hold the key to a patient's condition, and House's friendship with Wilson is tested beyond limits as murky memories from the bus accident the night before threaten to change their lives forever.