The character of Molloy in Homer the Vigilante was based on actor David Nivens' performance as a gentleman thief in the film Raffles - and who better to play the role than everyone's favorite kid-hating paleontologist?
Wow, Meryl Streep really CAN play any role, huh? She can even pull off a conniving 10 year old preacher's daughter. During their recording sessions together for Bart's Girlfriend, Nancy Cartwright had wanted to get Streep's autograph, but was afraid to ask. After their recording session, Streep revealed her kids were big Simpsons fans and asked Cartwright for her autograph.
Brooks was an early supporter of the show, having guest-voiced numerous characters since the very early years. Originally, Scorpio was going to be the primary villain of The Simpsons Movie - but was eventually replaced (disappointingly) by the character Russ Cargill, also voiced by Albert Brooks.
In Lisa's Wedding, Mandy Patinkin (who isn't British) played the very British future almost-husband of Lisa.
When The Simpsons includes a celebrity appearance, they almost always are able to get the actual celebrity to do the voice - and in the rare case they can't, they have one of their regular voice actors step in for the impersonation. Yet they brought in comedian Jay Mohr to voice Christopher Walken in Insane Clown Poppy after Christopher Walken cancelled his own recording.
The character was named after writer Mike Scully's two daughters, Allison and Taylor.
Frank Welker appeared over 20 times on The Simpsons, always voicing animals, including the elephant Stampy, Lisa's pony Princess, Laddie, the bus gremlin, and Werewolf Flanders. Thank goodness the voice of Megatron is so versatile.
The top choices for the voice of the Space Coyote in El Viaje Misterioso de Nuestro Jomer (The Mysterious Voyage of Homer) came down to Johnny Cash and Bob Dylan. Since Bob Dylan had previously rejected opportunities to appear on the show, the role was offered to Johnny Cash, who accepted.
The ballet teacher (who is never named) was designed to look like Sarandon after she accepted the role.
Dafoe was one of showrunner Josh Weinstein's favorite guest stars ever to appear on the show.
Douglas was not the writers' first choice for the role of Itchy & Scratchy creator Lampwick - it was William Hickey they originally wanted, but he declined the offer. Douglas was a famously difficult guest voice - he refused to use the recording room earphones, so it became difficult for the vocal director to give him notes (Nancy Cartwright, the voice of Bart, ended up taking on most of his directorial duties). He also refused to do more than two takes per line.
After appearing in season 3 in the episode Colonel Homer, D'Angelo would return to the role 16 years later for the episode Papa Don't Leech.
Mrs. Glick has appeared several times since her initial appearance in Three Men and a Comic Book, but her later appearances (some even after the character had died) were voiced by Simpsons regular Tress MacNeille.
The original cut of the episode was running a little too long, so they brought Jeff Goldblum back into the recording booth to re-record all of his dialogue at a slightly faster pace.
All of the Simpsons' writers showed up to Pfeiffer's recording session for The Last Temptation of Homer, a rare occurrence.
After originally appearing as Homer's half-brother in Season 2's O Brother, Where Art Thou?, DeVito returned twice - in season 3's Brother, Can You Spare Two Dimes? and Season 24's The Changing of the Guardian.
After voicing Maggie's first word in Lisa's First Word, Elizabeth Taylor later guest-starred on The Simpsons the same season as herself for Krusty Gets Kancelled.
After originally appearing in Mother Simpson, Close would return to the role a few more times, for Season 15's My Mother the Carjacker, Season 19's Mona Leaves-a, and Season 23's How I Wet Your Mother.
In addition to voicing Akira in One Fish, Two Fish, Blowfish, Blue Fish, George Takei also voiced Wink in Thirty Minutes Over Tokyo and the Chinese waiter in The Old Man and the Key.
Here's a weird one - Michael Jackson guest-starred in the episode Stark Raving Dad, playing Leon Kompowsky, a man who seemingly believed himself to be Michael Jackson, yet wanted to keep his involvement a secret, so was credited as "John Jay Smith." While Jackson provided the speaking voice, his singing voice was done by singer Kipp Lennon (a sound-alike, so that Jackson could play a prank on his brothers, seeing if they would be able to tell it was not him).
Leon Kompowsky's normal voiced was then done by Hank Azaria for the end of the episode, meaning three different people voiced the same character in a single episode.