The episode begins with Gideon sitting in on the presentation of a book written by retired profiler (and Gideon's mentor), Max Ryan. He wrote the book about an unsolved case (the Keystone Killer) from 20 years prior (the one that got away). After the presentation, they are talking when a security guard approaches Ryan with an enveloped addressed to him. It turns out to be a note from the unsub from Ryan's book.
The Keystone Killer case occurred in Philadelphia. The unsub killed seven women, and then all of a sudden stopped. The police and FBI had no idea what had caused him to stop murdering. When the unsub brings the letter for Ryan, it contained the driver's license for an Amy Jennings (whom had been his last victim in the 80s) and one for a Carla Bromwell (whom the team later finds out is a new victim).
The unsub had changed his methodology, going from strangling with his bare hands and using a rope tied with an intricate knot; to hitting his victim over the head, suffocating them with a plastic bag, and binding them with flex cuffs. This confuses the team, along with the reason he had stopped killing for 20 years.
Ryan refuses to work with the team, preferring to work solo as he had back when the initial case was being investigated. This is worse after they arrive at Carla Bromwell's home where Reid and Hotch find a note from the unsub, in which he uses a quote Ryan's book. He eventually comes around to the team concept, after several conversations with Gideon and watching the team at work. He probably saw how well they worked together.
They arrive at the conclusion that the unsub did not choose to change his method of killing, but was forced to due to health problems or an accident. When Reid tells them that "in the U.S. there is a car accident occurring every 10 seconds," they start focusing their search on car accidents starting in 1988 because car accidents are reported by the police.
They find one person who was in a serious accident that injured his spinal cord, Walter Kern. He had been military and most recently had installed home alarms. Because of severed nerves, he lost most of the use of his right arm. Upon searching his home, Reid, Ryan, and Gideon discover that Kern's victims had been targeted all along because he had been on his way to Carla Bromwell's when he had his accident. His accident occurred in the area of her residence. They find out the next victim, and they race over to her house and rescue her.
The episode ends on the plane with Ryan telling a story of one of Gideon's first cases, and Elle and Hotch having a heart-to-heart about life and the job. She tells Hotch how she was afraid that she would wake up one day and find that her life had passed her by, and asks how he has a wife and a baby. Hotch tells her he makes his family his first priority when he's with them, and the team first when he's working. "It's all a matter of setting priorities and keeping them." He also tells her the job would eat her up if she let it, and that she had to find a way not to let it.