A patient is admitted after breaking out in a severe rash triggered by caustic chemical exposure at his blue-collar job. As the team treats him, they discover that he has led his wife to believe that he is still maintaining his once-lucrative real estate career. Meanwhile, Cuddy is honored with an award and needs House to be at the charity event for support, but his attendance is threatened when his patient’s battle to survive forces him to question his practice and his own happiness, and Chase and Masters teach each other a lesson in forging meaningful personal and professional relationships.
House participates in a school’s Career Day and breaks a few rules by sharing explicit medical stories. Waiting outside the principal’s office, he meets two fifth-grade students who assess House’s relationship woes and try to help him understand how his selfish antics get in the way of showing Cuddy how he really feels.
When a waitress with a perfect memory suffers temporary paralysis, her older sister visits her in the hospital, which triggers high stress levels and even more health complications. The patient’s sharp memory proves detrimental when a grudge she’s been holding against her sibling gets in the way of receiving proper medical treatment, and Masters discovers that patching a broken sisterhood may prove to be more complex than diagnosing the patient. Meanwhile, Foreman volunteers to help Taub prepare for a medical examination, while House, determined to help Wilson get back in the dating scene, discovers Wilson’s secret new companion.
Cuddy’s mother, Arlene, is admitted to Princeton Plansboro after complaining about unusual symptoms, but stubborn Arlene insists that House be removed from the case, forcing House to come up with non-conventional – and illegal – means to treat his patient. House instructs his team to follow his lead, and they discover details in Arlene’s personal life that she kept secret from Cuddy and her sister Lucinda. Meanwhile, Taub’s ex-wife, Rachel, puts him in contact with her brother who hires Taub to work a job on the side in exchange for much-needed income, which winds up taking a physical and emotional toll on him. Later, Cuddy places her trust in House to ensure that her mother receives the proper medical treatment, leading “by the book” medical student Masters to reevaluate her responsibility to practice within a code of ethics and to follow her boss’ orders.
House and the team try to link symptoms of a teenage military recruit and his drill sergeant; House secretly helps Cuddy's daughter get into a prestigious preschool; someone posted a disparaging photo of Chase on a social-networking site.
After a 200-year-old medicine jar found on an off-shore shipwreck shatters in a teenage girl's palm, she is admitted to Princeton Plainsboro for symptoms closely linked to smallpox. When the Center for Disease Control's Dr. Dave Broda institutes a lockdown on the hospital and suspends House's team's ability to diagnose, Masters grows suspicious of Broda's motives and becomes convinced that the patient is suffering from a different disease. The girl's father soon experiences similar symptoms, and House is forced to make a precarious decision that puts his own life in jeopardy. Meanwhile, Wilson and Sam comfort a 6-year-old chemotherapy patient who prompts them to examine their relationship.
Science and faith are called into question when a patient is admitted to the hospital following his reenactment of the Crucifixion. Meanwhile, Taub questions his wife, Rachel, about her relationship with an infidelity support group member, and the team attends a co-worker's wedding where Wilson's relationship with Sam takes an unexpected turn.
It’s election season, and in the midst of a tight campaign, an incumbent New Jersey senator’s campaign manager falls ill with liver failure and temporary paralysis. Cuddy pushes House to add a female doctor to his team by hiring brilliant third-year medical student Martha Masters in Thirteen’s absence. House and the team are wary of the young doctor’s lack of experience and medical perspective, but are forced to give their new by-the-book teammate a chance to prove herself. After the campaigning senator makes a surprising announcement, House and the team look to the candidate to find clues about the patient’s condition. Meanwhile, Foreman learns that Taub has a past connection to Masters, and in an effort to save his patient’s life, House must make a critical decision that may compromise his relationship with Cuddy.
When an infant suffers breathing trouble and liver failure, House and the team must look at the medical history of the mother in order to find an answer, and ultimately land on a discovery that forces the mother to jeopardize not only her child's health but her own. Meanwhile Taub and Foreman must find a new female doctor to fill the spot vacated by Thirteen and House and Wilson learn a thing or two about parenting while caring for Cuddy's daughter.