A death row inmate is felled by an unknown disease and House decides to take on the case, over Cuddy and Foreman's objections. House also has to deal with Stacy who is working closely with him, while Cameron has to cope with a dying patient.

A 16-year old high school student, Dan, starts suffering from nightmares and frequent hallucinations, and he reveals he was hit in the head while playing lacrosse at school. Dan is apparently suffering from MS, and risky brain surgery is needed. Meanwhile House must deal with a patient looking to set up a lawsuit and a mother who doesn't believe in vaccinations.

During an meningitis outbreak which overwhelms the clinic, House is drawn to a single patient: a 12-year-old whose symptoms don't quite match everyone else's. House, Foreman, and Chase must devise ingenious ways and locations to treat the girl's delicate condition in the middle of the chaos, and make an unexpected discovery. Meanwhile, House asks Cameron to come back to her job but she has one requirement that he might not be able to meet.

When Stacy insists her husband Mark get tests, House insists he can handle things. But despite the fact Mark's tests prove negative, his steadily growing symptoms indicate he is dying. While House struggles with the mystery and make increasing demands on his staff, Wilson worries about House's emotional well-being, and Cuddy considers adding a new employee to the clinic.

A college student collapses after rowdy sex with his girlfriend. While House and his team attempt to determine the cause, the student's condition continues to deteriorate and his symptoms multiply complicating the diagnosis.

When a virus is spreading among the hospital, infecting six babies, House and his team must make decisions that could compromise the lives of the babies.

House apparently triggers a stroke in a clinic patient, but the major topic of discussion is House's imminent date with Cameron, The team must deal with the patient's odd lifestyle, overbearing "friend," and reluctant parents in order to stop the strokes and try to save his life. Meanwhile, Wilson, Cuddy and the team offer House and Cameron advice while laying odds on the outcome.

House's ex-girlfriend Stacy Warner returns – not for House but to get help for her ailing husband. While House decides whether or not to take her case, Cuddy forces him to present a lecture to a class of medical students. As he weaves the stories of three patients who all present with a similar symptom, House gives a lecture the students will never forget.

When a high school student falls victim to a mysterious but lethal poisoning, House and his team jump in to find out what is killing the teen. Given a low heart rate and a clean tox screen, House sends Cameron and Foreman to the teen's home to find the hot new drug House is sure he's taking. They don't find any drugs, but think they've come up with the answers, until a second unrelated student is admitted with identical symptoms. With the boys' lives hanging in the balance, House and the team have to connect the dots – fast. Meanwhile, an 82-year-old patient has become enamored with House while he helps her figure out the basis of her renewed fascination with her sexual feelings.

Legendary jazz musician John Henry Giles is checked into the hospital and when he's told he's dying from ALS, he signs a DNR to avoid a slow death. House disagrees with the diagnosis and goes against everyone's wishes when he violates the DNR to save Giles' life. The decision lands House in court, drives Foreman to consider taking another job, and results in Giles' paralysis worsening. But when the patient inexplicably starts getting better, the team has to figure out the mystery in reverse and find out why his condition is improving. Meanwhile, Dr. Foreman meets with an old friend who offers him a West Coast partnership.

Dr. Foreman believes an uncooperative homeless woman is faking seizures to get a meal ticket at the teaching hospital. But her homelessness strikes a personal chord with Dr. Wilson and he grows determined to keep her from falling between the cracks. Her worsening symptoms prove to be a complex mystery for House and his team, but the mystery of her identity and medical history may hold the answers to saving her life. Just as the team suspects she has contagious meningitis, the woman goes missing, only to be tasered by the police, who bring her back. But House deduces the taser may have proven yet another diagnosis, with dire results. Meanwhile, House has an audience of two medical students who are learning how to do case studies.

While trying to figure out why a young patient won't stop bleeding after a car wreck, House takes Cuddy's challenge and goes off Vicodin for a week in exchange for no clinic duty for a month. If House and his team can't determine the source of his patient's blood loss, the 16-year-old car victim will die in a matter of days. As House's withdrawal symptoms become more and more severe, his patient directives for his patient are more harsh and risky than usual, and Foreman and Cameron are afraid he may not be thinking clearly enough to save the patient's life.