A Cuban couple attempt to get to America by raft... to see House about the wife's heart condition. But when she gets worse House wonders if someone on his staff messed up. Meanwhile Foreman prepares to leave and his departure threatens to shake up the entire team.

Masters faces a career crossroads on her last day as a medical student and struggles with the choice to continue on the path to become a surgeon or to accept the rare opportunity to join House’s team officially. Meanwhile, the team treats a 16-year-old girl who inexplicably collapsed days before embarking on an ambitious sailing tour around the globe. Despite the patient's life-changing diagnosis, the patient's family insists on getting her back on the seas in time for her potentially record-breaking launch. But to the team's surprise, including House, Masters makes a bold decision regarding the patient’s treatment.

After losing a bet with Wilson over a boxing match, House is convinced that his fighter has an underlying medical condition that cost him the fight. While he tries to prove it, he leaves his team alone to help a bomb scientist who suffered a seizure. Meanwhile, House may be experimenting with a new drug to help his leg pain.