- Dakota Fanning, in one of her earliest roles, played a molestation victim in Season 1’s “Blood Drops”.
- Misha Collins, Season 5 Episode 13 “Nesting Dolls”, as Vlad
- Marcia Cross, most notable for portraying Bree Van De Kamp-Hodge on Desperate Housewives appeared in the episode “Organ Grinder” from the second season.
- Clueless star Stacey Dash played a “newbie” lab tech who flirted with Warrick in “Slaves of Las Vegas” from Season 2.
- Kelly Rowan (Melinda Clarke’s co-star on The O.C.) also appeared in “Slaves of Las Vegas” as Eileen Nelson, the wife of a man who hated her. He made a girl from an underground fetish club act like her, and his violence resulted in him killing her. Coincidentally, Clarke and Rowan appeared in the same episode prior to working together in ‘The O.C.’, though they did not appear in scenes together.
- The Usual Suspects star Steven Baldwin appeared as Jesse Acheson, who was investigated in Season 5’s “Compulsion”.
- The Who frontman Roger Daltrey guest starred as a missing mob boss who comes back to Las Vegas to pay back his would be killers in “Living Legend”, season 7.
- Ugly Betty and Disney Channel star America Ferrera had a guest starring role in the season 5 episode “Harvest”.
- Frank Gorshin made his last ever TV appearance in “Grave Danger”, the season 5 finale.
- Faye Dunaway played a prominent ex-showgirl and mob mogul’s former flame in the episode “Kiss-Kiss, Bye-Bye” in season 6.
- Danny Bonaduce appeared as Izzy Delancy, the Miniature Killer’s first victim, in the two-part Season 7 opener “Built to Kill” as well as “Loco Motives”.
- Kevin Federline made his guest appearance in season 7, starring as a street hoodlum known as ‘Pig’ leading a gang of college kids in carrying out random, brutal and sometimes fatal beatings on a citizen and mainly tourists throughout Las Vegas. This episode sees the gang seriously assaulting Greg Sanders when he tries to intervene on one of their vicious attacks. Kevin’s character is also seen shouting abuse at Nick and Warrick while they are investigating the scene of Sanders’ attack, this subsequently lead to physical altercation between Nick and Kevin’s character ‘Pig.’
- Ned Beatty made a guest appearance in the episode “Sweet Jane” in season 7, playing a serial killing dentist.
- Lost stars Ian Somerhalder, Josh Holloway, Elizabeth Mitchell, M.C. Gainey and Harold Perrineau have all guest starred. Somerhalder portrayed a murder suspect name Tony Del Nagro in 2002 in “Revenge Is Best Served Cold”. In 2003 Holloway played Kenny Richmond in “Assume Nothing,” a casino valet who was Nick’s college baseball teammate. Both episodes were the third and fourth season premieres respectively. Mitchell appeared as Melissa Winters, a wheelchair-bound prosecutor and friend of Sara’s with a deadly secret in “One Hit Wonder”, and Perrineau played a reverend with a sordid past and an exorcism patient who is missing in “Go To Hell”.
- Before becoming a regular on CSI: NY, Carmine Giovinazzo made a guest appearance in “Revenge Is Best Served Cold”, making him one of the several actors to be in all three CSI shows.
- Summer Glau of Firefly & Terminator: The Sarah Connor Chronicles played Mandy Cooper in the episode “What’s Eating Gilbert Grissom?”.
- Juliette Goglia played Hannah West, a child prodigy who muddied the waters in two murder cases her half-brother was involved in. Her cold, calculating actions made Sara Sidle rethink her career choice and she left at the end of the episode “Goodbye and Good Luck.” Sara left her duty vest for new CSI Ronnie Lake, after removing her name tag and throwing it into the garbage. The first was “The Unusual Suspect” in season 6.
- Constance Marie played detective Carolina Flores in “Two and a Half Deaths” from the eighth season
- Guest appearances have been made by no less than four of The Shield cast members, namely: Catherine Dent (Danny) in “Who Shot Sherlock?” Season 5 (as the killer), Kenny Johnson (Lem) in “Time of Your Death” Season 6 (as the driver of the Corvette), Walton Goggins (Shane) in “Empty Eyes” Season 7 (as the killer), and Jay Karnes (Dutch) in “For Gedda” Season 8 (as the IA Detective).
- Jamie Hyneman and Adam Savage of MythBusters appeared as scientists-observers in the Season 8 episode “The Theory of Everything”.
- Kay Panabaker acts as Catherine Willows’s daughter Lindsay assuming the role after Madison McReynolds left the show.
- Pauley Perrette acts as an aspiring singer who befriends Catherine Willows’ husband in Lady Heather’s Box.
- Ally Sheedy as Sharon Turner in episode “Leapin’ Lizards (CSI)”.
- Method Man, as Drops, appears in the episodes “Poppin’ Tags”, “Big Shots” & “Drops Out”.
- Taylor Swift as Haley Jones in the March 5, 2009 episode.
- Holt McCallany was in the episode “Young Man with a Horn.” He previously played Det. John Hagen on CSI: Miami.
- Heroes star Milo Ventimiglia played Bobby in the Season 1 episode Friends & Lovers.
- The Office (U.S. TV series) star John Krasinski appeared in the Season 5 episode Who Shot Sherlock.
- Travis Barker played a rapper in an episode about East Coast/West Coast Wars.
- Shanna Moakler Former Miss USA appeared in the same episode as now ex-husband Travis Barker.
- Carlos Alazraqui as a Reno cop in Let it Bleed (a nod to his role in Reno 911!).
- Allison Scagliotti-Smith known for her role in Drake & Josh as Mindy Crenshaw played a fast food restaurant employee in the episode “Deep Fried and Minty Fresh”.

