After House’s medical license is reinstated, he reclaims his role as Head of Diagnostics in time to treat Hank Hardwick, an adult film star admitted to Princeton Plainsborough for pulsating eye pain. Meanwhile, Cuddy is reminded that Princeton Plainsborough is not conducive to healthy personal relationships.
When a controversial African politician falls ill, he is brought to Princeton Plainsboro for treatment. The team struggles with whether to help a merciless dictator being subpoenaed for crimes against humanity in his country. Meanwhile, Wilson tries to make peace with a feuding neighbor, but House’s prying exacerbates the problem.
A wealthy businessman brings his teenage son, who is suffering from inexplicable stomach pains, to Princeton Plainsboro and insists on having Dr. House handle the case. The father of the patient believes the karmic penalty of his financial success is that he is victim to personal tragedy, and that the answer to his son's medical mystery lies in a reverse of fate rather than medical treatment. Meanwhile, Foreman and Chase prepare to present information on the Dibala case.
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. The team must use their imaginations to carefully choreograph ways to test and treat her delicate body without killing her. Meanwhile, House continues to suffer from what he thinks is insomnia, and he is willing to go to desperate measures to cure it.
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.
House returns home to Princeton where he continues to focus on his recovery, but surprises Cuddy with the news that he's making a big change in his life. Meanwhile, the team is unable to diagnose a loud-mouthed video game creator who posts each new symptom on the internet and opts for treatments suggested by the online community rather than by the doctors, and Foreman angles for House's job, but the pressure to solve the case creates tension in his relationship with Thirteen.
Charlotte, an older woman who has spent the last six months taking care of her dying husband Eddie, is rushed to Princeton Plainsboro after collapsing from respiratory failure. The couple becomes a double mystery for the team when Eddie begins to improve as Charlotte’s condition worsens. The previously unthinkable becomes real when it seems that Charlotte will die before Eddie, and the team will be forced to make a difficult decision.
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. Since she pushed him to take the case so emphatically, House forces Cameron to take the lead and run many of the tests on the patient. Meanwhile, House is unsure of Wilson’s new healthy diet.
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