Prentiss and Jordan Todd go undercover in Atlanta, Georgia, to profile a serial killer who has perfected his skill as a pick-up artist and uses his masculine prowess to lure his next victims. Meanwhile, Morgan begins teaching Reid tricks on how to charm women.
- Julianne Anderson - Young Vanessa Holden
- Jon Barton - SWAT Leader
- Sarah Belgrad - Bar Patron
- Joanna Cassidy - Mrs. Holden
- Cutter Cutshaw - Transforming Unsub
- Roxy Darr - Paul's Girlfriend
- Shelley Dennis - Becky Williams
- Stephanie Edmonds - Girl in Blue Dress
- Courtney Ford - Austin
- Meta Golding - Agent Jordan Todd
- Currie Graham - Paul Thomas
- Mitch L. Guy - Club Dancer
- Spencer Hill - Richard
- John Karyus - Pickup Artist Student
- Riki Lindhome - Vanessa Holden
- Rachael Markarian - Ringer Girl
- Marcia Moran - Mrs. Parker
- Jake Newton - James
- Gabriel Olds - Robert Parker
- Kimberlee Peterson - Melissa Foster
- Steffinnie Phrommany - Model
- Keri Lynn Pratt - Ashley Holden
- Curt Roland - Young Robert Parker
- Cari Shayne - Detective Rachel Harding
- Geneva Somers - Brandi
- "Make U Wanna Dance" by Gen Rubin
- "Suspicious Character" by The Blood Arm
- "Around Here" by Peri
- "28 Butts" by Little Jackie
- "Back to You" by Puddu Varano
- "Million Dollar Baby" by Phontaine
- Emily Prentiss: Author Harlan Ellison wrote, "The minute people fall in love, they become liars."
- David Rossi: P.J. O'Rourke said, "Cleanliness becomes more important when Godliness is unlikely."
- The title probably refers to both the unsub's habit of picking up his victims and the "card game" of the same name, which is sometimes used to teach children to pick up after themselves. In 52 Pickup, which is often "played" as a joke, one player tosses a deck of 52 cards into the air and the other picks them up, referring to the unsub's habit of disemboweling his victims and making them clean up the mess it leaves.
- Cari Shayne previously costarred with Thomas Gibson on the made-for-TV movie The Inheritance, in which they starred opposite each other as lovers.