A case involving a serial killer believed to be copying Jack the Ripper takes Gideon to New Orleans after three victims are found with their throats cut. Once thought to have been killed in Hurricane Katrina, the discovery of a fourth victim in the French Quarter confirms the murderer is still alive. All the evidence and files had been lost in the flood, so the only clue the team has is the word "Jones" that the lead detective wrote on the wall just before he drowned. Meanwhile, Reid meets up with an old rival as he continues to struggle with the aftermath of being held hostage.
In this conclusion of a special two-part episode, finding the serial killer becomes critical to the BAU when the team realizes Reid is being held captive and a live feed of him being tortured is shown on the internet. Meanwhile, Reid's troubled childhood is revealed in flashback sequences as he drifts in and out of consciousness.
Gideon is pitted against the scariest and most evil murderer in his entire career. When the BAU confronts the sadistic killer in a remote diner in the Nevada desert, the local authorities want to move quickly and make an arrest. But Gideon bides his time as he attempts to persuade the man, who has sworn not be captured, to reveal the whereabouts of a woman he is holding hostage.
The BAU is called to investigate a series of murders of prostitutes in Washington D.C. and Reid suspects a teenager he met asking for his help is guilty of the crimes. The case becomes complicated when a congresswoman, who about to make a speech to praise the city's lower crime rate, threatens to take away the case if Hotchner calls a press conference to discuss it.
Gideon, Reid and Prentiss travel to Guantanamo Bay to interrogate the leader of a terror sleeper cell being detained there after a chemical weapons dispersal device is discovered during a raid at a suspicious house. Working with Reid, Emily's fluency in Arabic proves to be useful as they scrutinize the suspect.
The daughter of high-powered diplomats, Special Agent Emily Prentiss joins the team, and she must convince Gideon and Hotchner she deserves the job based on merit and not on her family connections. The BAU is then called to St. Louis to investigate two serial killers who appear to be competing with each other. By setting a trap based on one killer's profile, the team creates a media event by which to capture the second killer.
The BAU travels to Seattle to identify and catch a serial bomber who has been terrorizing the city and targeting centers of automated techology. Working with the author of a science fiction novel that has become a guide for the bomber, the team attempts to determine why certain sites have been chosen as targets.
The BAU team continues to unravel the clues given to each of them by a psychopath in order to save his most recent victim. Gideon decides not to focus on the personal aspects of the case. Rather, he tells the team to profile the killer as they would in any other investigation. Reid stays behind to work on a personal connection that could solve the case as one member of the team fights for life.