In the season 2 finale, House suffered multiple gunshot wounds inflicted by a former patient's husband determined to carry out retribution for House's treatment of his wife's case. In a shocking surprise to his co-workers, House comes through the ordeal with a slightly new perspective on his treatment of patients - but will it affect how he makes medical decisions? And will it last?
House has recovered from multiple gunshot wounds and is back at work, taking on two cases simultaneously: Richard, paralyzed after brain cancer surgery eight years ago, who drove himself on his motorized wheelchair headfirst into a swimming pool; and Caren, a young woman paralyzed from the neck down after a yoga session. As House begins to diagnose and treat them, the team notices a distinct change in his attitude toward the patients.
Seven-year-old Clancy has been admitted to the hospital with rectal bleeding and claims of being tortured by aliens. The team runs tests on him, but when they get different results from the same tests, in addition to finding a metal object in his neck, they are forced to give Clancy's alien claims a little more credence. Amidst all this weirdness, Cuddy and Wilson decide it would be best not to tell House the truth about his last case, thinking that perhaps he will learn some humility if he believes that he is not always right. Cameron discovers the lie and is outraged. A frustrated House gives up on his young patient, forcing Cuddy to re-think her decision to hold back the truth.
House is back to using his cane and does not want to talk about it. His new patient is Ezra Powell (guest star Joel Grey), a renowned medical research pioneer who collapsed in his lab. House puts Ezra through diagnostic rigors, but the team is unable to come up with a conclusive diagnosis and Ezra's health continues to deteriorate. Becoming increasingly debilitated, Ezra ultimately demands that the team stop the litany of medical tests and help him end his life. The team members have divergent opinions on the morality of helping Ezra die, especially since the possibility of a cure is still in question. Meanwhile, the teenage daughter of a clinic patient has developed a disturbing crush on Dr. House.
House takes the case of Adam, a 10-year-old severely autistic boy who screams loudly for no apparent reason. Cuddy makes a minor change to House's office and House refuses to use the office until it is returned to its original state; he thus finds himself wandering the hospital in need of a temporary home, crashing in Cuddy and Wilson's offices. Meanwhile, teenager Ali from the previous episode still has a crush on House and is becoming a nuisance around the hospital.
House takes the case of a young woman who has been rushed to the hospital with problems breathing and severe stomach pain after she and her husband were robbed. After her husband collapses, the team believes the couple's illnesses are related. Meanwhile, Michael Tritter, a clinic patient, causes problems for House.
A morbidly obese man is found in a coma and admitted to the hospital. Upon waking, he demands to be discharged, and refuses to be tested for any disease possibly caused by his weight.
House decides to awaken a comatose patient so he can question the man regarding the family history of his son, who may have a genetic condition and the father is the only living relative. Meanwhile, Wilson confronts House about the stolen prescription pad as Tritter approaches Cameron, Chase, and Foreman in an attempt to divide the team and reveal their loyalties.
House's newest patient is 18-year-old Jack, brought to the hospital after experiencing a heart attack and massive vomiting. Jack has been the parent to his younger brother and sister since their parents died. After a brief review of his file, House thinks he has got the diagnosis, seals it in an envelope and turns the process into a game, challenging Cameron, Foreman and Chase to figure it out on their own. Meanwhile, in an attempt to extract a confession, Tritter makes it almost impossible for Wilson to practice medicine, driving a wedge between House and Wilson.
House and the team take on the case of Alice, a young girl with pancreatitis. Since her divorced parents cannot agree on how to proceed with her treatment and will not let House bully them into making a decision, House's only option is to take them to court and let a judge rule on the matter. Meanwhile, House's reduced access to Vicodin is beginning to take its toll and he asks Cuddy for more of the medication, but instead of writing a prescription, she strictly rations his pills.
It is Christmas at Princeton-Plainsboro and Wilson has a present for House. He and Detective Tritter have struck a deal and House has three days to accept it. Cuddy receives a patient afflicted with dwarfism, who has a variety of symptoms and is recovering from a recently collapsed lung, and House takes on the case. Cuddy is eventually forced to make a difficult and potentially life-threatening choice between her patient's life and House's life.
House is forced to respond in court to the criminal charges against him regarding illegal possession of narcotics, and the judge sets a date for a preliminary hearing. Cuddy insists that House apologize to Detective Tritter. Meanwhile, the most recent case at the hospital is a firefighter suffering from disorientation and extreme body temperatures. Because of misinterpreted information, the firefighter is eventually forced to make a decision to undergo a radical brain treatment which will have a serious effect on his life.
House has beaten the drug charges and is back at the hospital after a short stint in rehab. Tired of House's disdain for patients, Cuddy turns his clinic duty into a game, with the stakes raised to a level that speaks to House: challenge. There, House encounters Eve, who has tested positive for an STD and admits she has very recently been raped. She refuses to be treated by anyone but House. Cameron encounters a homeless man who is very different from how he originally seemed.
16-year-old Stevie Lipa is admitted to Princeton-Plainsboro with a serious respiratory condition and internal bleeding. He is assigned to House, but House is busy fulfilling a dare given to him by Cuddy. A startling secret is revealed about Stevie, and the team encounters troubles with his parents. Foreman is forced to ask Stevie to lie directly to his parents, risking his medical license.
A girl (Mika Boorem) with the rare inability to feel pain gets in a car accident. Once her testing is done, she begins having high fevers with multiple seizures and is rapidly deteriorating.
A brain-damaged music savant (Special Guest Star Dave Matthews) has seizures despite being on anti-seizure medications, while everyone is shocked to learn that House has entered himself for brain cancer treatment.
House treats a US Marine returning from Iraq, who has symptoms consistent with Gulf War Syndrome. House's dream about the Marine complicates his handling of the case.
A famous, pregnant photographer, Emma Sloan, is brought to the hospital after suffering a stroke in the middle of a photo shoot with Tyson Ritter. Although Emma's condition initially stabilizes, her health takes a turn for the worse when her kidneys fail. As her health continues to deteriorate, Emma is more concerned about her baby's well-being than her own. Meanwhile, the secret relationship between Cameron and Chase is exposed to Foreman and Cuddy, and House makes extravagant plans to take a much-needed vacation.
House and Cuddy face a widespread outbreak on their plane back from a symposium in Singapore while Wilson and the team treat a woman with constant seizures.
A six-year-old girl suffers ailments expected in much older patients. Tensions between Chase and Cameron lead House to intentionally assign them to the same tasks, including investigating the young girl's home.
A scam artist loses her ability to make decisions. While House and the team struggle to find the underlying cause, the case becomes personal for Foreman.
A 14-year-old leukemia patient's only hope of survival is a bone marrow transplant from his younger brother. But when he gets sick, the team must race against time to save both kids. Meanwhile, Foreman must deal with the consequences of the previous patient's death.
Speculation over Foreman's resignation continues, while a young girl named Addie is admitted after bleeding from the mouth during martial arts practice. House and Wilson are secretly concerned about each other.
House meets his match in the form of Nathan Harrison, an obnoxious 16-year-old chess prodigy with intense head pain and behavioral issues, who manages to annoy and offend every member of House's team during his course of treatment. Meanwhile, Foreman's frustration with House reaches a new level when he believes House sabotages his job interview with another hospital.
House and the team take on the case of a young woman who, along with her husband, is rescued at sea en route from Cuba in a desperate attempt to see House and get a diagnosis for her illness. During her stay in the hospital, she develops a new symptom: her heart stops – but she keeps talking. Meanwhile, Foreman prepares for his last day at Princeton-Plainsboro Teaching Hospital.