The BAU presents one of the longest-tenured serial killer cases to an undergraduate Criminology college class, and they take the class through a seventeen-year-long chase for the murderer. Meanwhile, Rossi deals with personal demons concerning the case.
- Jolie Adamson - Georgina Yates
- René Ashton - Grace Powell
- Eugenia Care - Marie
- Denise Carole - Crystal
- Kay D'Arcy - Trudy Yates (2009)
- Julie Dove - Brianne Matloff
- Paul Morgan Fredrix - Donald
- Eileen Fogarty - Doctor Lin
- Alec Gatlin - Thomas Yates (Age 10)
- Daniel Guzman - Doctor Castro
- Richard Henning - John
- Sally Hughes - Devin
- Elizabeth June - Professor Marsha Grant
- Linda Sandee Larson - Lynn
- Ashley Leggat - Sloan
- Kelly Lynn Warren - Trudy Yates (1977)
- Cyndi Martino - Diane
- Kellen McGee - Angie
- Adam Nelson - Thomas Yates
- Dan Owens - Steve
- Kagiso Alicia Paynter - Bianca
- Thomas Phelan - Thomas Yates (Age 15)
- Tara Shayne - Tina Dyson
- Elizabeth Southard - Becca
- Shannon Sullivan - Ruth Taylor
- Nate Thomas - Lance
- Zack Weinstein - David Zimmerman
- Richard Ramirez, The Night Stalker (mugshot only)
- Jeffrey Dahmer, The Milwaukee Cannibal (mugshot only)
- John Wayne Gacy, The Killer Clown (mugshot only)
- Aileen Wuornos, The Florida Highway Killer (mugshot only)
- Andrei Chikatilo, The Rostov Ripper
- Efren Saldivar
- David Parker Ray, The Toy Box Killer
- John Edward Robinson, The Slave Master
- David Rossi: The philosopher Voltaire wrote, "To the living, we owe respect. But to the dead, we owe only the truth."
- David Rossi: Irish statesman and author Edmund Burke once wrote, "The only thing necessary for the triumph of evil is for good men to do nothing."
- Eileen Fogarty, the actress who portrays Doctor Lin, previously starred as a woman in an episode of Suspect Behavior, the short-lived Criminal Minds spin-off.
- It is erroneously stated that the episode's unsub was the most prolific serial killer the BAU had ever seen, despite the fact that they had encountered at least two killers with body counts topping his prior to the episode.