After admitting their deep attraction for each other, both House and Cuddy try to get away from the pressures of the hospital by spending some vacation time together at the beach. Remarkably, they both start feeling far less miserable than either of them has felt in years. However, when secrets from both of their pasts come to light, it threatens their nascent relationship.

A family copes with a sick daughter and a dying son, and the team must diagnose the daughter before it's too late. Meanwhile, House deals with an elderly father and son, and tries to deal with the challenges of a workplace romance.

House and his team must treat both the physical and psychological ailments of a popular children's author when she collapses just moments before attempting sleeping. When the diagnosis proves difficult, House becomes motivated as he believes the answer to her problems lie within her latest novel, which he happens to be a fan of. Meanwhile, House and Cuddy go on a double date with Sam and Wilson.

A patient is admitted to Princeton Plainsboro suffering from uncontrollable vomiting. In the process of treating her, House and the team make some unexpected discoveries about her identity and are forced to look at her medical history in order to learn the truth about her past. Meanwhile, House gives a less than friendly welcome to Chase's new hire and a visit from House's massage therapist causes trouble between House and Cuddy.

After a newborn experiences inexplicable breathing problems and liver failure, House and the team look at the baby's mother, Abbey's, own medical history for possible clues. When the team makes a discovery about her newborn's health, Abbey is presented with a difficult decision that could potentially affect both her baby's health and her own. Meanwhile, following Cuddy's directive, House challenges Foreman and Taub to hire a female doctor to join the team. When Cuddy asks House to babysit her daughter, both House and Wilson learn a few hard lessons in parenting.

In the midst of a tight senatorial re-election race, the New Jersey incumbent's campaign manager mysteriously falls ill with liver failure and temporary paralysis. After a surprising campaign announcement is made by the incumbent, 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.

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.

House and the team must treat a man who collapsed after risking his life to save a stranger who fell onto the subway tracks, but it appears that there is more to this good deed than meets the eye. Meanwhile, House tries to avoid a birthday dinner with Cuddy and her mother, and Taub gains some unexpected attention and gets some help with his personal life from Martha Masters.

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.

When Cuddy's mother is admitted to Princeton Plainsboro and wants House off the case, House must come up with non-conventional methods to treat her. In the process he uncovers secrets which Arlene has hidden from Cuddy and her sister Lucinda.

Masters tries to mend the rift between a patient with perfect memory and her sister, when the patient's grudge threatens her treatment. Meanwhile, House tries to help Wilson get a date but discovers that his friend already has someone, and Foreman offers to help Taub study for an upcoming medical exam.

After House traumatizes a fifth-grade class with explicit medical stories during Career Day, he's sent to the principal's office and two students offer him relationship advice.

A patient is admitted to Princeton Plainsboro after breaking out in a rash caused by chemical exposure at his job. In the process of treating the patient, House and the team learns the man's wife still believes he runs a lucrative real estate business.

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.

The team treats a professional bullfighter who is attacked by a bull. The team must determine the causes behind the patients disappearing symptoms and seizures while taking House's advice from outside the hospital as he attends to issues unrelated to the case. Meanwhile, Masters develops a crush on the patient.

A young homeless man with a history of drug abuse (and a secret) arrives at the hospital with bad burns and scars on his chest. Meanwhile, Cuddy tells Wilson that she feels guilty about breaking up with House.

House's encounter with an ex-employee who's disappeared for a whole year reveals some dark secrets hidden; meanwhile, the team must find a cure for a man whose house is filled with junk.

House and the team treat a teenage girl who collapses just before embarking around a potentially record-breaking boating trip around the world. Meanwhile, Masters must decide if she wants to continue her schooling in order to become a surgeon or accept an offer to stay on House's team permanently.

After suffering partial paralysis while searching for a long-lost love, lottery winner Cyrus Harry is brought to Princeton Plainsboro for treatment by House and the team. Cuddy's mother threatens to sue the hospital for malpractice, jeopardizing both Cuddy and House's medical licenses.

The team takes on the case of a missile design expert suffering from a wide variety of symptoms. She fails to show improvement and the team looks to House, only to discover that he's obsessed with the case of a boxer who collapsed during a fight.

Hadley's prison cellmate comes to her for help when she receives a knife wound. However, her condition soon grows worse and Hadley calls in Chase for help. Meanwhile, House takes extreme measures to remove the tumors growing in his leg, while Taub receives news from his girlfriend and takes it poorly.

The team treats an esteemed performance artist, but discover that she wants to perform a new piece using House as her unwilling assistant. Meanwhile, House vows to change, but when Cuddy and Wilson insist that he talk out his feelings, he takes a radical approach to making a new life for himself.