When an office building collapses, House has to work fast to diagnose a young woman, Megan (Bevin Prince),^[13] who has managed to survive the disaster. Without a team, House talks through his ideas with a janitor at Princeton-Plainsboro. As House persists in diagnosing Megan by himself, he soon realizes the case is not what it appears to be and that solitude may not be the answer.

House systematically begins eliminating his new team candidates, until he is approached by a fighter pilot named Greta (Essence Atkins),^[15] a candidate for NASA's astronaut training program. Greta suffers from a neurological disorder, where she converts sounds to visual images. Knowing NASA will reject any possibility of her becoming an astronaut if they knew of her problem, Greta begs House to treat her in secret. Meanwhile, House is ruffled when he thinks he sees Cameron, Chase and Foreman in the hospital hallways.

The final ten fellowship candidates compete ferociously against each other when House splits them into two teams by gender. They are assigned to diagnose and treat a wheelchair user (Brian Klugman)^[17] with spinal muscular atrophy who is slowly suffocating. As the teams try to outdo the other, complications arise. Meanwhile, Foreman runs his own team at another hospital, and resorts to using a very "House-like" treatment to help a patient.

While having a seizure, a funeral home cosmetician (Azura Skye)^[19] hallucinates she is being violently raped by one of the cadavers. When she is admitted to the hospital, she acts as though her dead mother is in the room with her. While Cameron offers advice to one of the remaining candidates for House's team, a recently fired Foreman has lunch with Cuddy, discussing his current situation.

Foreman returns to Princeton-Plainsboro and is assigned to oversee House's candidates. A man (Frank Whaley)^[21] is mugged and suffers from a respiratory arrest. Though he has no memories of who he is, he can read the personality of the most dominant person in the room, applying it to himself to create a temporary identity. This is due to a rare disease known as Giovannini Mirror Syndrome. House becomes intrigued by the accuracy of this judge of character and manipulates the patient to judge others, while a team member wonders if House is more dominant than Cuddy.

House is recruited by the CIA to help diagnose a deathly ill agent (Joel Bissonnette).^[23] The agent's case is spearheaded by Dr. Samira Terzi, who offers very little information on the agent's history or previous assignments. With limited information, House uses some unorthodox methods to try to determine a diagnosis in time to save his patient's life. Meanwhile, Foreman faces a huge uphill battle from the remaining fellowship candidates when they start questioning his judgment while arguing over the proper diagnosis of a female drag car racer (Amy Dudgeon)^[24] who passes out after a race.

House and his team are followed by a documentary film crew as they treat a teenager (Khleo Thomas)^[26] with a major facial deformity, who suffers a heart attack prior to a reconstructive procedure. As they work to diagnose the teen, House finds himself distracted by several of the candidates vying for a spot on his team, causing him to question his own motives for having chosen them.

House encounters a magician (Steve Valentine)^[28] whose heart fails when performing an underwater escape act. While the remaining fellowship candidates work to diagnose him, House is determined to prove he is a scam artist faking his ailments to cover up the fact he nearly drowned during his act. In the meantime, House pits his team against one another in a challenge involving Cuddy, granting the winner immunity from elimination and a chance to nominate two other candidates to be put on the chopping block.

Final diagnosis: Autoimmune hemolytic anemia in systemic lupus erythematosus

House assigns the candidates to a particularly challenging case involving an uncooperative punk guitarist (Jeremy Renner) with a history of drug abuse and civil disobedience, while Cuddy orders House to make a final decision and hire his new team. House promises a guaranteed position for the candidate who correctly diagnoses the patient. Meanwhile, Wilson informs a former patient he misdiagnosed him with terminal cancer and is now going to live and must deal with the consequences of his procedures.

House and his new team composing of the three lucky applicants, Chris Taub, Lawrence Kutner and Thirteen treat a woman (Janel Moloney)^[31] who suffers from a sudden paralysis of the hands, causing an injury to her daughter while she is watching 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, he becomes convinced that the mother is withholding information.

When Dr. Cate Milton (Mira Sorvino), a psychiatrist trapped in the South Pole and the research station's only doctor, becomes ill in the middle of her assignment, she and 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. Meanwhile, House sends Taub, Kutner and Thirteen to harass Cameron until she gets cable for his office and he attempts to discover the identity of Wilson's new girlfriend. This episode originally aired in North America, outside of its regular time slot, immediately following Fox's broadcast of the Super Bowl XLII post-game show.

Final diagnosis: Fat embolism from unrepaired broken toe

House and the team encounters a woman (Laura Silverman) admitted to Princeton-Plainsboro after she collapses at her wedding. Her test results come up negative for a variety of common diseases, which leads the team to suspect foul play, but when they discover the woman is a former music producer living in the fast lane until she began to practice Hasidic Judaism, House insists people do not change, and her seemingly rash decision may be a symptom of the underlying condition.

Final diagnosis: Nephroptosis

House suspects an emergency room patient (Paul Rae)^[34] 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 is at odds with Wilson's girlfriend, Amber, 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 (Jason Lewis) has a serious medical condition, after observing his symptoms on television. He decides to intervene and take matters into his own hands, but both the actor and House's team dismiss his assessment and do not believe there is anything wrong. Meanwhile, Wilson and Amber 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 is convinced through his flashbacks a fellow bus passenger is exhibiting signs of a deadly illness prior to the crash. Much to the team's dismay, House pushes through the pain of his injuries, desperate to piece together the fragments of his shattered memory in order to save someone who might not even know he could be dying. And once he learns the truth, he and his team are left shellshocked when it's discovered that Amber Volakis, Wilson's girlfriend, is the one who's dying.

As the team rushes to find the underlying cause of Amber's injuries, clues inside House's head may hold the key and House's friendship with Wilson is tested as memories from the bus accident the night before threaten their relationship. Meanwhile, Thirteen struggles to cope with her own personal health problems whilst treating Amber.