Showrunner Al Jean chose Peyton Manning as a guest star for this episode after seeing his performance on a season 32 episode of Saturday Night Live. Coincidentally, Peyton's brother, Eli, cameoed in that episode, and later, guest hosted for the 2011-2012 season.
Charlie was designed to resemble Fry from Futurama (his red jacket and hair claw in particular), Matt Groening's other creation, making Bart and Charlie brothers of a sort.
The title of this episode is also the title of a season two Gossip Girl episode.
Bart's vision of what life would be like in years to come if he had another sister is a spoof of Sex and the City, and Kim Cattrall (one of the stars of the series) even plays the imagined third sister.
Strangely, Homer and his half-brother Herb (who was only featured twice in the series) don't make it into Bart's dream, even though Bob and Cecil, the latter of which was also featured twice in the series, do.
The Smith Brothers coughing then taking cough drops is a reference to the fact that the brothers were famous purveyors of cough drops, and, well over a century later, their product is still one of the most popular brands.
Wilbur Wright saying "I want a turn! I want a turn!" while following the plane, which is being piloted by Orville, is a reference to the fact that Orville piloted the first flight of the Wright Flyer, with Wilbur following on foot.
Peyton and Eli Manning's teasing of Cooper is a reference to the fact that Cooper never got drafted by an NFL team, while Peyton and Eli went on to become Super Bowl-winning quarterbacks with the Indianapolis Colts and the New York Giants respectively.
The song that plays at the start of Bart's "Bro-Town" dream sequence is "Everybody Get Together" by The Dave Clark Five.