Before the filming of the season began, it was announced that A. J. Cook had been let go from the series, reportedly due to budget cuts on the show relating to the launch of the Criminal Minds spinoff.

In the season premiere "The Longest Night", Tim Curry reprised his role as one of the series' most notorious criminals, Billy Flynn, also known as "The Prince of Darkness".

Sally Kirkland guest-starred as May Walden, a famous actress from Hollywood's Golden Age who, because of her pregnancy, made only one motion picture, and her career was ruined afterwards.

Angus Macfadyen guest-starred as Sean McCallister, Emily Prentiss' former boss at Interpol who is murdered by one of the series most notorious criminals, Ian Doyle, played by Timothy V. Murphy.

In the episode "The Thirteenth Step", Jonathan Tucker and Adrianne Palicki guest-starred as Raymond Donovan and Sydney Manning, two young lovers who go on a killing spree.

In the episode "With Friends Like These", Bug Hall guest-starred as Ben Foster, a schizophrenic spree killer who, after burning down a church, begins hallucinating three people who died there.

In the episode "Hanley Waters", Kelli Williams guest-starred as Shelly Chamberlain, a spree killer who is unable to come to terms with the death of her son, who died in a car crash.