Hoynes' line about his alcoholism - "I liked beer a little bit too much in college." - may reference actor Tim Matheson's previous role as a drunken lout in the classic movie Animal House.
Abigail Bartlet makes a Sesame Street appearance to mollify the public about her having resumed medical work after voluntarily surrendering her license in the wake of a political scandal over her misusing it. Talking with the president's secretary about the Muppets' impending arrival, Abbey makes various knowledgeable remarks about the distinctions between the casts of Sesame Street and The Muppet Show, likely a reference to actress Stockard Channing's having appeared in several of the "Mad Painter" sketches on Sesame Street in the 1970s.
Toby: There were maybe four people in the room when I had that conversation.
Will: Well, if I'd have been one of them, I would have repeated it to everyone I met.
Which is exactly what he did on an episode of Sports Night a few years prior:
Isaac: Things that I say in my office stay in my office.
Dana: Natalie's my second-in-command, she's the only one I told.
Natalie: Jeremy's my boyfriend, he's the only one I told.
Jeremy: I told many, many people.
But I Play One on TV: After the first season, people around Hollywood started treating Martin Sheen like he was the President for real.
The Character Died with Him: John Spencer's death from a heart attack was written into the show. Several episodes where he was still alive aired after Martin Sheen's tribute to him before one episode, and the in-universe death occurs on "Election Night".
Flip Flop of God: Regarding the series finale. Lawrence O'Donnell said that the original plan was to have Vinick win, but after John Spencer's death they changed it to Santos to make it easier on the audience. John Wells, however, says this wasn't the case.
The last season saw the election of Matthew Santos as POTUS, Santos's character was based on Barack Obama after the show's creators met him while still an Illinois state senator. The real life "Josh" (Rahm Emmanuel) also took over as Chief of Staff.
Santos' Republican opponent Arnold Vinick was loosely based on John McCain - Southwestern Senator with bipartisan appeal. The mind-blowing thing is that Santos and Vinick run in 2006... two years before the Real Life election of 2008, and when there was no guarantee that either Obama or McCain would win their respective nominations (The front-runners in 2008 were Hillary Rodham Clinton and Mitt Romney).
In "Welcome to Wherever You Are", there's a brief scene where we overhear a Vinick ad using the slogan "Yes, America Can", which the Santos campaign complains was actually their slogan. Obama's slogan, of course, ended up being "Yes We Can".
Reality Subtext: Ron Silver switched parties from Democrat to Republican between his character's appearances on the show.
Alda and Smits in season six-seven. James Brolin in season three-four.
Not to mention Martin "President Bartlet" Sheen.
Another example would be Matthew Perry's casting as a White House counsel (although he predictably fit in rather well). Christian Slater, on the other hand....
Technology Marches On: The show started off with beepers and accordion envelopes. By the fourth season everyone has a cell phone and... well the accordion envelopes were still there, just with computers on top of that, too.
Throw It In: CJ's performance of The Jackal. Allison Janney used to use it to entertain her castmates.
Kristin Chenoweth (Annabeth Schott) was originally approached to play Ainsley Hayes but could not commit to a television series due to Wicked.
Sidney Poitier was considered for the role of The President. Alan Alda and Jason Robards were also possibilities.
Sorkin intended Zoe's kidnappers to be domestic terrorists, which was why Nancy McNally said that it was probably a cheap-shot operation in the episode when it happened, and there were many incidents with domestic terrorists throughout the season. The new showrunners went with generic Muslim terrorists who were mad about Sharif.