In the episodes, President Josiah Bartlet deals with multiple crises, including a cover-up of the assassination of a foreign dignitary, while Josh Lyman, Toby Ziegler, and Donna Moss attempt to return to the White House after they are accidentally left behind in Indiana.

Much of the episode deals with the trio's attempts to get home; however, their journey is delayed by several mishaps (Cathy's truck runs out of biodiesel, they miss their plane due to confusion over Indiana's time zones, they board the wrong train, etc.)

Josh and Toby remain largely oblivious to the problems of the people around them, until they meet Matt Kelley, an affable man in a bar who is concerned about how he's going to pay for his daughter's college tuition.

Meanwhile, an exhausted and overworked Sam Seaborn is supposed to be taking the day off for some much-needed sleep, but Josh instead enlists him to staff the President until they return from their escapade in Indiana.

On May 6, 2006, NBC Sports aired a special program before the Kentucky Derby that plagiarized two passages from the speech that Sam writes for the President following the explosion of the pipe bombs in "20 Hours in America, Part II".