Dana Delaney, who guest-stars in the two-parter "Tick...Tick...Tick...Boom!" is a multiple Emmy winner who was once a fixture on lists of the most beautiful people in Hollywood. Most tropers watching this show will probably recognize her as Lois Lane (leading to the always weird effect of Lois-sounding dialogue coming from the un-Lois-looking Delaney's mouth), or Katherine Mayfair, where Nathan Fillion played her husband.
Which gives a new layer of meaning to Nathan's line "Except for my second wife, this is the most sexless relationship I've been in."
"A Deadly Affair" has Wendy the waitress show up as the wife of one of the murder victims.
"Little Girl Lost" has Carla as the mother of the lost girl.
"3XK" has Drew from the last series of Scrubs as a suspect's terrified ex prison roommate who is in actuality the serial killer who masterminded the episode's killing in order to escape prison, as well as Marshall Darling as the father of a serial killer's cold-case victim.
"Always Buy Retail" has Hardison as a Nigerian immigrant.
Azazel appeared in Castle's supernatural-themed Halloween episode, where characters talked about ghosts and demons. Azazel himself finds the idea of demons to be ridiculous. He turned out to be the killer.
Lee Garner, Jr. is one of the people holding up a bank in "Cops & Robbers."
Arrow's John Diggle (David Ramsey) plays an elementary school teacher in season 2's "Fool Me Once".
Hey, It's That Place!: Sort of. The warehouse that they fight the murderer in "Boom!" in returns again in "Setup," with absolutely nothing to disguise it and several shots of the warehouse which are basically exactly the same in both episodes. Either they ran out of locations or the terrorist in setup used the same warehouse again. Lampshaded by Castle when he wonders why that particular building is so popular.
The hallway leading to the sleazy boyfriend's apartment in "Pretty Dead" seems very familiar - especially its distinctive square window.
They don't even try to hide the fact that the hangar they use in "Secret Santa" is the same hangar that was used for the climax of "Knockout".
Castle didn't actually go very far in his pursuit to retrieve Alexis in France. They use the same church in "Hunt" as the one previously used in "Always".
I Want You to Meet an Old Friend of Mine: Some of the people that help Castle and the 12th also happen to be people Nathan Fillion has worked with in the past, most notably Dana Delany in "Tick Tick Tick"/"Boom!" and Kristen Lehman in "Eye of the Beholder." Castle's first wife, Meredith, is played by Darby Stanchfield, who also played his wife in Waitress. Alyssa Milano is also apparently a friend of Nathan's, but the two haven't worked together except for "A Rose for Everafter." "Headhunters" finally brought a Firefly alumnus to the table in the form of Adam Baldwin. Gina Torres gets in the game in "Reality Star-Struck". Still waiting on the others! A minor one in Reality Star Struck (aka the one with Zoe), but notable as being between two guest stars, rather than a guest star and a main cast member: Patrick Fabian plays the reality show director, and Lachlan Buchanan plays the son of one of the show's stars. They previously worked together on the CMT sitcom Working Class.
Real-Life Relative: Kevin Ryan's (Seamus Dever) girlfriend/fiancée/wife, Jenny O'Malley, is played, when she appears, by Dever's real-life wife Juliana.