Aaron Sorkin based the character of Sam Seaborn (Rob Lowe) on George Stephanopoulos, President Bill Clinton's Communications Director and 1992 campaign adviser.
It is mentioned that the Roosevelt Room is named after Theodore Roosevelt. The Roosevelt Room is, in fact, named after both Presidents Roosevelt. Normally, when Democrats control the White House, the portrait of Theodore Roosevelt is replaced with the portrait of Franklin D. Roosevelt.
During Josh's first scene in the pilot, the camera pans over his desk's inbox, in which there is a copy of "George" magazine with Josh's (Bradley Whitford's) face on the cover. George was a real magazine, started in 1995 by John Kennedy Jr. and his business partner, Michael J. Berman. The magazine strove to cover politics in a celebrity- and popular culture-driven way; it folded in 2001, about a year and a half after Kennedy's death.
The Lambs of God are based on a real life group "The Lambs of Christ".
The Press Briefing Room shown early in the pilot is a different set than the one used in subsequent episodes.