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The BAU investigates a spree killer in Philadelphia and is led to the city's boxing scene in search of the unsub. Also, Hotch makes a connection with an attractive runner as they both train for a triathlon.
- Jill Alexander - Doctor Joanne Carlton
- Abby Brammell - Pam Hall
- Tim Davis - Jason
- Charles S. Dutton - Tony Cole
- Matt Fleuret - Joe
- Sandra Genovese - Billie
- Shawn Hatosy - Jimmy Hall
- Ken Lally - Jack Messmer
- Ludwig Manukian - Doctor Raj Surna
- David Mazouz - Ryan Hall
- Roman Mitichyan - Flashback Boxer
- Marcus Natividad - Boxer #1
- Jessen Noviello - Monty
- Sean Kathryn O'Connor - Doctor Jean Bellamy
- Richie Parker - Boxer #2
- Jeremy Radin - Man
- Kelsey Scott - Paramedic
- Gustin Smith - Boxer #3
- Ray Stefanelli - Referee
- Benny Urquidez - MMA Referee
- Torrey Vogel - Frank
- Mark Withers - Lou Manzoni
- Bellamy Young - Beth Clemmons
- "Turn a Light On" by Kathryn Calder
- Aaron Hotchner: "Everybody wants to go to heaven, but no one wants to die." — Joe Lewis
- Aaron Hotchner: Hermann Hesse wrote, "Some of us think that holding on makes us strong, but sometimes it is letting go."
- The episode's title seems to be a play on the term "The Sweet Science", which was coined by British sportswriter Pierce Egan as a nickname for boxing.