- Diahnna Nicole Baxter - E.R. Doctor
- Bodhi Elfman - Peter Lewis
- Lauryn Kennedy Hardy - Maya Walker
- James Levine - Howard Nathanson
- DeRon Munroe - Eli Walker
- Andrew Pifko - The Doctor
- Dean Schaller - Shirtless Man
- Josh Stewart - William LaMontagne, Jr.
- Tracie Thoms - Monica Walker
- "Burden" by Foy Vance
- Spencer Reid: "Hold on when there is nothing in you except the will which says, 'Hold on!'" – Rudyard Kipling
- "Wheels Up" is a phrase used by Hotch – and, eventually, Prentiss in a minor capacity – to announce the departure of the team's jet.
- Damon Gupton is removed from the main cast. His character died at the end of season twelve
- Daniel Henney joins the team, replacing Damon Gupton
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