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. Cameron and Chase get married. House admits himself to a detox program.

House and the team take on the case of a ballerina whose lungs collapse in the middle of a performance. When the treatment causes her skin to fall off, the dancer faces not only the prospect of never dancing again but also of dying an agonizing death. Meanwhile, House continues to suffer from a severe lack of sleep and is still haunted by Amber. While enlisting Wilson's help to diagnose himself, he is willing to do the unthinkable to make his visions stop.

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. 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.

Cameron postpones her vacation with Chase in order to ask House to accept the case of an environmental radical who collapsed at a protest with unexplainable symptoms. Although suspicious of her motives, House agrees. Meanwhile, House is unsure of Wilson's new healthy diet.

Charlotte, an older woman who has spent the last six months taking care of her husband Eddie, is rushed to Princeton Plainsboro for immediate treatment after collapsing from respiratory failure at Eddie's deathbed. With both in the hospital, the husband and wife team becomes a double mystery when Eddie's condition sporadically improves while Charlotte's condition deteriorates. 

Dr. Lawrence Kutner dies of suicide using a gun without any explanation why. While most of the cast grieve, House tries in vain to understand why Kutner died. 

We find ourselves inside the mind of Lee as he awakens after a bicycle accident in New York unable to move or communicate verbally. From his unique perspective, we hear Lee's inner thoughts as House, injured in a motorcycle accident, occupies the hospital bed next to him. Meanwhile, Wilson suspects House is hiding something from him when he refuses to divulge why he was in New York when he got into his motorcycle accident.

House and the team take on the case of Morgan who works in a nursing home with a pet cat who only sleeps next to people if they are about to die - and does so with alarmingly accuracy. When it seems the cat has predicted her own death, Morgan, convinced she is about to die, fakes a seizure in order to get to House to have him diagnose her before it's too late.

House and the team take on the case of Nick, a book editor who loses his inhibition and starts insulting coworkers at a dinner party one night before falling ill. Meanwhile, House suspects Wilson and Taub are keeping something from him when he catches them both in a lie. House is determined to get to the bottom of it.

The team encounters a teenage boy who collapsed from severe pelvic pain after playing basketball. Tests reveal the boy has genetic mosaicism, or both male and female DNA, and the boy's parents inform House and the team that the boy is unaware of his condition.

When a priest who runs a homeless shelter sees a bleeding Jesus hovering at his doorstep, he is admitted to the ER. House takes on the case as a distraction for the team while he confronts Foreman and Thirteen about their relationship.

House and the team take on the case of a woman who collapsed in the middle of a cooking class, and they soon learn she is a highly-renowned cancer researcher who recently gave up her entire career in order to pursue her own personal happiness. As the patient's condition continues to worsen, so does Thirteen's as she begins to suffer serious and life-threatening reactions to the experimental Huntington's Disease clinical trial.

Cuddy decides to spend more time at home to take care of her newly adopted baby and passes some of her day-to-day responsibilities off to Cameron, including supervising House. Cameron is forced to play House's games and becomes involved in a power struggle as he and the team take on the case of a Special Education teacher who collapsed after spitting up blood in the middle of class.

At Cameron's urging, House and the team take on the case of a man living with such severe chronic pain that he tries to kill himself, unable to go on after living for years without a diagnosis or any relief from his suffering. Meanwhile, Foreman and Thirteen explore their now complicated relationship as they work together on the Huntington's disease clinical drug trial, and Cuddy finds that taking care of her newly adopted baby leaves her little time to run a hospital and baby-sit House at the same time.

House and the team encounter a teenager who collapsed during her high school Christmas program. Foreman continues to work with Thirteen on the Huntington's disease drug trial, and their relationship progresses when he learns a valuable lesson from her. House gives a clinic patient an unbelievable holiday gift and keeps the team guessing about who may have sent him a particularly thoughtful Christmas present. Meanwhile, Cuddy receives an unexpected gift of her own.

House and the team take on the case of a high-profile fitness trainer who collapses while shooting an infomercial. Meanwhile, Thirteen begins her participation in a clinical drug trial for Huntington's disease led by Foreman, Kutner sets up and runs an online medical advice clinic under House's name and Cuddy moves into House's office while hers is being repaired, much to the dismay of her new officemate.

A gun-wielding man from the waiting room at the Princeton-Plainsboro clinic takes House, Thirteen and several patients from the waiting room hostage in Cuddy's office. The man claims to be sick with a long undiagnosed illness and demands medical attention from the best doctor in the hospital, threatening to kill any hostages necessary along the way.

The team takes on the case of a 16-year-old factory manager who fell ill when her lungs suddenly filled with fluid while at work. Meanwhile, Foreman asks for House's permission to work on a clinical trial and House rejects his proposal. In an effort to prove himself capable of working without House's supervision, Foreman takes on his own pediatric case. But when the unexplained illness brings the child to the brink of death, Foreman is left questioning his ability to work free from House's custody.

When an agoraphobic man falls mysteriously ill and adamantly refuses to leave his home to get treatment at the hospital, House and the team go to him to figure out what might be wrong.

The team takes on the case of a dreary middle-aged man who has been experiencing unexplained recurring blackouts and time lapses. Meanwhile, House finds out Cuddy is going to adopt a baby that is due in two weeks.

When a woman with whom Thirteen had a one-night stand falls ill and has a seizure at Thirteen's apartment after a night of partying, Thirteen accompanies the woman to Princeton-Plainsboro where House and the team take on her case. Meanwhile, House keeps his private investigator, Lucas hot on Wilson's trail.

When House receives word that his father has passed away, he brushes off the news and dismisses the idea of going to the funeral. However, he is soon coerced into going despite his strongest protests. Back at Princeton-Plainsboro, the team encounters the case of a young woman adopted by American parents who collapsed while in China looking for her birth parents.

House and the team take on the case of a struggling artist who has been painting bizarre portraits. His undiagnosed illness is distorting his perception, threatening to undermine his career, his relationships and everything else in his life. House continues to have a private investigator dig up dirt on everyone on his team.

When several people die suddenly and without warning five years after receiving transplants from a single organ donor, House and the team rush to save the only two surviving recipients. House has hired Lucas Douglas, a private investigator, to dig up information about the deceased despite the team's skepticism. Meanwhile, House auditions new best friends to replace Wilson, and soon uses Lucas for his own personal means to spy on Wilson and the other team members.

Eight weeks after the death of his girlfriend, Amber, Wilson is still mourning her death, and his relationship with his best friend House is shattered. Needing to make a change in his life and give himself time to recover emotionally, Wilson resigns from Princeton-Plainsboro. The team must push forward as they encounter a case involving an assistant to a high-profile executive, who is a textbook "Type A" personality.