Dr. House exasperates his boss, Dr. Lisa Cuddy, when he suggests that two sick newborn babies in one hospital add up to an epidemic. Even more frightening is the fact he may be right. As more babies are quarantined and the maternity ward is shut down, Cuddy power-scrubs the hospital and House spars with Dr. Cameron and his team of specialists over his plan to possibly sacrifice one sick baby for the good of the others.
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.
House treats a 15 year old faith healer, while Wilson feels left out when he finds out House has a weekly poker game.
After a wild night out, a teenage girl is brought to Princeton Plainsborough with severely swollen appendages. The team must work to diagnose the young girl, who is less than honest about what happened the night she fell ill. As her condition worsens, she becomes unable to distinguish fact from fiction. Meanwhile, Cuddy, Wilson and House spend a weekend away from the hospital to attend a medical conference, but things don’t go as planned when House’s private investigator, Lucas returns.
Wilson prepares to transplant bone marrow from Matty to his brother Nick. But when Matty gets sick, the team must cure him as he’s the only safe donor. Meanwhile Foreman deals with the consequences of his mistake and House has a battle of wills with his new pet Hector.
Tension reaches new heights when Cuddy faces sobering news that propels her to reevaluate her priorities. While House is distracted by his concern for Cuddy’s well-being, the team treats a teenage patient whose worsening symptoms and suspicious body scars indicate more than just physical illness.
House and the team take on the case of a 22-year-old minor league hockey player who collapsed while coughing up blood after a fight on the ice. Meanwhile, House drops a bomb on Wilson, and Chase offers to help Park change her living arrangement.
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.
House and the team are intrigued by Scott, a man whose left brain and right brain operate independently, leaving him with two distinct personalities and no control over some of his actions. As the two sides of Scott’s brain struggle for dominance, his warring personalities make it increasingly difficult for the team to figure out what is causing the unique problem. The team is forced to use some unusual methods to get him to cooperate with their necessary testing. Meanwhile, when House refuses to make an appearance in the clinic, Cuddy takes an unconventional approach to force House to make up the time with a particular patient.
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 engages in a battle of wits and wills against the attending physician in charge of his detox program. When he starts to lose, House resorts to blackmail to gain the upper hand.
Thirteen brings her one-night stand to the hospital after the woman has a seizure. However, the woman admits she slept with Thirteen just so she could get to House and have him diagnose her condition. Meanwhile, House continues to pay Lucas to spy on Wilson.
The team takes on the case of a deaf 14-year-old named Seth who collapsed after he started “hearing” explosions while competing in a wrestling match. When the team tries to test him for seizures, Seth loses vision in one eye, complicating House’s bunk theory of “Exploding Head Syndrome.” As his condition worsens, the team has an ethical disagreement about the patient and his mother’s adamant decision to forego cochlear implants to supplement his hearing. When the prospect of giving Seth the ability to hear for the first time in his life arises, House and the team are faced with a resounding decision. Meanwhile, House’s lack of sleep starts to play tricks on his mind, but he finds his insomnia may be a gift instead of a burden
House has to work fast when a woman comes in with a life-threatening case of insomnia. Meanwhile Cameron is angry at Foreman for stealing an article she worked on.
When a famous professional cyclist is brought in after collapsing during a race, House doesn’t want to treat him because he thinks he’s lying about doing drugs. But when the patient is forthcoming about taking all sorts of performance enhancers and blood-doping drugs, House is definitely intrigued. Cameron is upset the patient is a hero to kids when he is clearly cheating at his sport. She struggles with the ethical dilemma of patient confidentiality and considers going to the media. Meanwhile, House tries to disrupt Stacy and Mark’s relationship by attending a group therapy session with Mark.
The team deals with an organ donor whose organs prove fatal, and the two surviving patients. Meanwhile, House hires a private detective to spy on Wilson, but hears a few things about himself that he’d rather not.
An 18-year-old teenager is brought to the hospital after having a heart attack. House reviews the boy’s file and believes he has the diagnosis. He then turns the case into a game by sealing his opinion in an envelope and challenging Cameron, Foreman, and Chase to guess House’s diagnosis on their own. Meanwhile, Tritter’s actions against Wilson continue to strain the oncologist’s relationship with House and destroy his ability to practice medicine.
House insists he can handle things when Stacy, the woman he once loved, asks him to diagnose Mark, the man she married. When Mark’s tests come back normal yet symptoms show that his brain is dying, the puzzle may be one that even House can’t solve.
While Wilson worries about House’s emotional well-being, the team is blown away by his over-the-top demands. As House struggles to put his emotions aside and solve the case, Cuddy adds to his dilemma and offers Stacy a reason to stay.
House and his team deal with a bullied girl who collapses during her school’s Christmas program. Meanwhile, Foreman and Thirteen grow closer during the Huntington’s disease drug trials, House gives a patient a gift, the staff wonder who gave House a special gift, and Cuddy gets an unexpected gift.
When young wife Elyse falls ill with a rare disease she can’t possibly have, Dr. Cameron is very interested in the case – so much so that her interest convinces House to take the case, and the team struggles to save her and appease her very attentive husband, Ed. After Dr. House and Dr. Wilson treat a woman at the clinic with new breast implants, the idea that House’s new patient Elyse may have breast cancer is raised as a possible diagnosis. But that diagnosis fails to be the answer when Elyse lapses into a coma after starting treatment. House starts to suspect Elyse has contracted a rare sexually transmitted disease, but when Ed and Elyse are questioned individually, they each deny having an affair. To save their patient’s life, the team has to acknowledge that House is right: everybody lies.
