- In the 1993 special For Our Children, co-host Baby Sinclair introduces guest performer Woody Harrelson by saying "he works in a bar" (referencing his stint on Cheers as bartender Woody Boyd).
- In the 1984 episode "I Call Your Name", Diane describes Sam as "a man whose idea of intellectual stimulation is to count along with Big Bird."
- In the 1986 episode "Take My Shirt... Please", Sam discusses his interest in PBS, particularly Bert and Ernie, "those two guys who talk about the day's events".
- In the 1987 episode "A House Is Not a Home" Sam and Diane are hosting one last Christmas for the Miller family as they have bought their house. One of the kids gets a Cookie Monster plush.
- Johnny Carson played himself in "Heeeeeere's... Cliffy!"
- Dick Cavett played himself in "They Called Me Mayday"
- Thomas Haden Church played Gordie Brown in "Death Takes a Holiday on Ice"
- John Cleese played Dr. Simon Finch-Royce in "Simon Says" (1987)
- Ted Danson played Sam Malone
- Kelsey Grammer played Dr. Frasier Crane
- Arsenio Hall played himself in "Where Nobody Knows Your Name"
- Pat Hingle played Gus O'Malley in "The Last Picture Show" (1993)
- Carol Kane played Amanda Boyer in "A Ditch in Time"
- Jarrett Lennon played Ludlow Tortelli in three episodes (1989-1992)
- Christopher Lloyd played Phillip Semenko in "I'll Be Seeing You" (1984)
- Bebe Neuwirth played Lilith Sternin
- Rhea Perlman played Carla Tortelli
- Markie Post played Heather Landon in "Just Three Friends"
- Michael Richards played Eddie Gordon in "Bar Bet"
- Frances Sternhagen played Esther Clavin
- Alex Trebek played himself in "What is... Cliff Clavin?"
- George Wendt played Norm Peterson
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