Dr. House decide investigar o caso de um presidiário condenado à pena de morte que sofre de uma misteriosa doença, mesmo contra a decisão de Cuddy e Foreman. Além disso, House começa a lidar com a presença de sua ex-mulher, que agora trabalha bem perto dele.

Foreman continua a apresentar sintomas semelhantes aos de um policial internado no hospital, acometido por crises de riso. House acredita que a solução para a doença esteja no apartamento do agente de polícia.

Após se recuperar dos ferimentos à bala, House está sem dor e anda sem ajuda da bengala. O médico volta a trabalhar, em dois casos: um homem de cadeira de rodas que tentou suicídio e uma mulher que ficou com paralisia após uma sessão de ioga.

House e sua equipe tratam um garoto que alega ter um rastreador alienígena em seu pescoço, além de ser cobaia de experiências desses aliens. Enquanto isso, Cameron se choca quando descobre que Cuddy e Wilson estão mentindo para House sobre o diagnóstico do último caso do médico mal-humorado.

A famous celebrity photographer suffers from a stroke while being pregnant at her early forties. House and his team have to deal with a great dilemma, save the mother or her unborn child.

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.

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.

The team takes 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.

A man awakens in New York after a bicycle accident unable to move or communicate in any way. House, himself injured in a motorcycle mishap, occupies the hospital bed next to Lee and quickly annoys the doctors treating them both by insisting that Lee has “locked-in” syndrome.

House is detoxing at a mental hospital and being held against his will by his attending physician, so he concocts an escape plan, aided by his roommate and a visitor named Lydia.

House and the team rush to treat an ailing college football star in time for the patient to compete in NFL tryouts. But when the patient experiences an onslaught of varied and unusual symptoms, the team has trouble reaching a consensus on how to effectively treat him in time. Meanwhile, Foreman’s brother Marcus makes a surprise visit to the hospital.

Cuddy, House and members of the team join forces with a search-and-rescue team to provide much-needed medical attention at the scene of an emergency.

When House discovers that the experimental drug he's been using causes fatal tumors, he decides to attempt to excise them himself. However, he can't complete the surgery and ends up needing Cuddy's help. Meanwhile, Thirteen's friend from prison (Amy Landecker), a relapsed drug user, arrives at her apartment needing medical care after being stabbed. With her friend unwilling to go to the hospital, Thirteen enlists Chase's assistance when the friend loses sensation and movement in her arm. Also, Taub receives some unexpected news that could change his life.

House and his team are placed under review after a staff member gets hurt.

The team takes on the case of Derrick, a 19-year-old college student who had a mysterious nose bleed during cheerleading practice, and discovers that his health issues are likely both physiological and psychological. Possibly suffering from schizophrenia, Derrick claims to hear his deceased brother’s voice in his head. Meanwhile, Foreman tries a different approach with House.