House and Cuddy are flying back to the US from an international conference in Singapore. While en route a mysterious disease strikes one passenger and an epidemic unfolds, causing House to diagnose in midair since they have missed the halfway mark by passing the north pole. Back in Princeton, Wilson and House's lackeys have a confusing case of what is ailing a woman who came into the clinic and proceeded to have a seizure.
A young girl is ailed with diseases that usually strike people much older than her 6 years of age. But before House can diagnose her, her brother starts exhibiting the same symptoms she was admitted with. During all of this House gives Wilson tickets that a patient had given to him for a play. Ensuing a discussion on why men take women to plays. Wilson decides to take Cuddy and the tug of war with House for her affections begins, although Cuddy insists that she only went with Wilson as a friend.
Wilson is preparing his 14-year-old patient, Nick, for a bone marrow transplant when the donor, Nick's younger brother Matty, suddenly starts sneezing. Since Nick's immune system has been destroyed by the chemotherapy for his cancer, he cannot risk a marrow donation from Matty while Matty is ill. House decides that the fastest way to find out what's wrong with Matty is to make him worse. As the boys get sicker and sicker, House and his team race to cure Matty before both brothers die. Meanwhile, House battles Hector (his newly adopted dog) for supremacy and Foreman ...
A 19-year-old college student, Addie, starts coughing up blood during karate class and ends up one of House's cases. Foreman hands in his resignation before treating the woman and refuses to explain why. Although her symptoms show no signs of it, House is convinced that an infection is causing Addie's bleeding. Her lungs start filling with fluid and House's team believes a toxin or cancer is to blame for Addie's illness but are unable to change House's mind. Addie continues to get worse and House wants to do an extremely risky life-or-death treatment in order to ...
House is forced to choose a new staff... and gathers 40 applicants to start narrowing down the field. Meanwhile, an Air Force pilot wants House to treat her secretly so she doesn't ruin her chances of becoming an astronaut.
Down to 10 candidates for his team, House splits them into 2 groups to diagnose a patient whose short lifespan has been made even shorter. Foreman leads his own team to diagnose a patient at his new workplace.
A victim of a mugging presents with neurological symptoms and begins to mirror the behaviors of his doctors. Foreman joins the new fellows in seeking a diagnosis; Cameron and Chase takes bets on whom House will fire next.