Plot: Nathan is released from the Chiefs, and struggles with a way to break the news to Haley and Jamie. As Peyton's delivery day approaches, Lucas and Peyton receive a surprise visit from Karen. Meanwhile, Dan finds himself on death's door, still waiting for a transplant; and Brooke and Victoria work to re-launch Clothes Over Bro's.

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Plot: Peyton and Lucas' wedding day arrives, and it's full of surprise guests. Haley winds up playing an unexpected role in the ceremony as Nathan waits for his call from the NBA. Meanwhile, after losing him at Lucas' first wedding, Skills keeps a close eye on Jamie the second time around.

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Plot: 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.

Plot: House is injured in a motorcycle accident in Middletown and finds himself in bed next to a patient suffering from complete paralysis. As House transfers the patient to Princeton to determine what's wrong with him, Wilson tries to find out why House was in New York.

Plot: While Julian makes Brooke a surprising offer, Lucas takes Nathan and Jamie to an important place from his past. Meanwhile, Peyton prepares for the future; Sam and Jack go up against the principal who fired Haley; and Skills and Mouth go on a road trip to help Mouth forget Millie.