Dean Norris, "F. Emasculata"
One of many future "Breaking Bad" stars to have first worked with Vince Gilligan on "The X-Files," Norris appeared in a Season 2 episode as a federal marshal trying to stop the spread of a nasty disease.
Jack Black, "D.P.O."
In Season 3, Black guest starred with Giovanni Ribisi as a teenager whose friend has the power to control lightning.
Ryan Reynolds, "Syzygy"
Long before "Deadpool," Reynolds played Jay "Boom" DeBoom, a jock murdered by a pair of psychic teen girls, on the third season of "The X-Files."
Lucy Liu, "Hell Money"
"Elementary" star Lucy Liu briefly appeared in a Season 3 episode about a Chinese black market for human organs.
Jodie Foster, "Never Again"
Though she didn't appear on screen, Foster provided the voice of a tattoo named Betty in a Season 4 episode.
Lili Taylor, "Mind's Eye"
In Season 5, Lili Taylor had a guest appearance as a blind woman who "sees" a violent crime and ends up accused of it herself.
Bryan Cranston, "Drive"
Famously linking Cranston to "Breaking Bad" creator Vince Gilligan, the Season 6 episode "Drive" starred the future Walter White as a horrible racist.
Ed Asner and Lily Tomlin, "How the Ghosts Stole Christmas"
In a Season 6 bottle episode, Asner and Tomlin played a pair of ghosts who haunt a mansion and turn couples against each other.
Shia LaBeouf, "The Goldberg Variation"
Shia LaBeouf appeared in a Season 7 episode as a bed-ridden boy suffering from severe liver problems.
Kathy Griffin, "Fight Club"
In Season 7, comedian Kathy Griffin played a pair of sisters who cause terrible things to happen when they're around each other.
Joe Morton, "Redrum"
Season 8 saw future "Scandal" star Joe Morton make a guest appearance as a man traveling backward in time.