House remains inhibited by injuries sustained from a bus accident that has also left a victim rapidly deteriorating from a mysterious condition. 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.

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.

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.

House suspects an emergency room patient has a bigger problem then the ER 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. 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 and the team encounter a woman 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. Meanwhile, House is preoccupied by Wilson's newly-outed relationship with a woman whose personality is remarkably similar to House's.

When Dr. Cate Milton, a psychiatrist trapped at the South Pole and the research station's only doctor, becomes ill in the middle of her assignment, she and Dr. House are thrust into a long-distance relationship of sorts. Unable to get Cate out or any additional medical supplies to the South Pole station, House and his team must resort to treating her via webcam.

House and the team treat a woman who suffers from a sudden paralysis of the hands that causes an injury to her daughter while she's spotting her at an indoor rock-climbing wall. As House probes the woman and her injured daughter for any leads as to what might be causing her condition, House is convinced that the woman is withholding information.

When Cuddy puts the pressure on House to choose the final members of his team, House deliberately assigns the candidates to a particularly challenging case - an uncooperative, over-the-hill former punk rock star with a history of drug abuse and civil disobedience.

House encounters a magician whose heart failed while performing an underwater escape act, nearly drowning. While the remaining fellowship candidates work to diagnose the illusionist, House is determined to prove that he's a scam artist faking his ailments to cover up his own incompetence. Meanwhile, House pits the fellows against each other in his version of an immunity challenge.

A documentary film crew chronicles a teenager with a major facial deformity who opts to undergo a dramatic reconstructive procedure. When the patient suffers a heart attack just before the surgery, House and the fellowship candidates must determine the cause since the surgery cannot proceed until the patient's cardiac condition is diagnosed. The film crew and the candidates, following around House, distract him. 
 

House is recruited by the CIA to help diagnose a deathly ill agent with an unknown illness. Meanwhile, Foreman faces resistance from the remaining six fellowship candidates when they question his judgment and argue over the diagnosis of a female drag car racer who passed out after a race.

The team takes on the case of a man who collapsed while being mugged. When the man complains of new symptoms that do not fit his initial admission profile, the team suspects he is a hypochondriac. As Mr. X continues to fall ill with symptoms unrelated to his neurological disorder, Foreman and the remaining six fellows are assigned to keep watch, and are bemused as they see their own behavioral idiosyncrasies reflected through him.

When a 20-year-old funeral home cosmetician, Irene, has a massive seizure, she hallucinates the cadavers in the funeral home have come to life, House and the remaining seven fellowship candidates must figure out why.

The final 10 fellowship candidates compete ferociously when House splits them into two teams by gender. They are assigned to diagnose and treat a wheelchair-bound man with muscular atrophy who is slowly suffocating.

House has relented to interviewing potential team members, but he's doing it his way. He called in all 40 applicants for the open three positions on his team and puts them to the test in a Darwinian trial period. As he drills the fellows and arbitrarily fires some along the way, an Air Force fighter pilot named Greta asks him to secretly treat her. She is a candidate for NASA's astronaut training program. House sets the applicants against one another to help treat the pilot with an unusual neurological disorder.

With his diagnostic team gone, House tries to diagnose Megan, a young woman who survived an office building collapse. Due to her injuries, Megan's only form of communication is blinking. With her condition worsening, Cuddy puts pressure on House to hire a new team, but instead, he attempts a differential diagnosis with help from the janitor. Wilson resorts to desperate measures by kidnapping House's guitar.