Michael J. Fox's final episode contained numerous references to his earlier series, Family Ties (1982), including a cameo appearance by Michael Gross (who played Fox's father in the earlier series), the doctor he plays has a secretary named Mallory, which was Fox's sister's name on the show, a reference to a Republican senator named "Alex P. Keaton" (Fox's earlier character) and Meredith Baxter starred as his mother, who also was his mother in Family Ties (1982).
In one episode Carter and Stewart go to a Rangers game and get a chance to compete in a shot from center contest, Stewart is the only person wearing a Detroit Red Wings jersey, a reference to Alan Ruck's role in Ferris Bueller's Day Off (1986).
In Young Guns (1988), Emilio Estevez, who is the brother of series star 'Charlie Sheen', shoots a man named Charlie Crawford, which is the name of Sheen's character here. Charlie Crawford is shot in one episode of Spin City.
The concept for the show was set in motion after the writers had seen Michael J. Fox in 1995's The American President (1995), playing one of the president's political aids. They wanted him to play a similar character for TV.
Tim Allen, Regis Philbin and David Letterman had cameos. They all voiced Rags the dog. Allen is the more memorable - while one character contemplates jumping out of a window, the dog talks, saying "Do it. And for God's sake, take me with you!"
Carla Gugino originally had second billing as reporter Ashley Schaeffer, carrying on a secret romance with Fox's character during the first season. She was subsequently written out to make Mike single, allowing more story lines.
Seven of the main cast members also starred in Scrubs (2001). Michael J. Fox - Dr. Kevin Casey ('My Catalyst' and 'My Porcelain God'); Richard Kind - Harvey Corman ('My New Friend,' 'My Fault,' 'My Malpractical Decision,' and 'My Female Trouble'); Barry Bostwick - Mr. Randolph ('My Dirty Secret'); Michael Boatman - Ron Laver ('My Roommates'); Alexander Chaplin/Gaberman - Sam Thompson ('My Moment of Un-Truth,' 'My Rite of Passage,' 'My Scrubs'); Heather Locklear - Julie Keaton ('My First Step' and 'My Fruit Cups') and Alan Ruck - Mr. Bragin ('My Lucky Day').