The team searches for a serial killer who justifies his crimes with paranoid religious motivation set on by a rapidly deteriorating medical condition.

Mr. Big phones Carrie and invites her to lunch, which she accepts against Miranda's advice. Samantha's sleep is being disturbed by the noise made by some transsexual prostitutes, and she ends up inviting them in for a rooftop party with the other three friends. Charlotte receives an early-morning visit from Trey, who's finally ready for her. Miranda is feeling that her life is in a rut, and runs into Steve on a couple of occasions.

An unstable woman stops taking medication and mows down 10 people with her car; a former rock star wages an anti-psychiatric drug campaign.

When the prolific serial killer Frank returns and murders Gideon's girlfriend, Gideon takes off to find him without telling the team where he is going. The BAU must then profile Gideon as well as Frank to find both of them.

When a heat wave hits Quahog, Peter gets Brian to enter a dog show to win $500 so that the family can get a new air conditioner. When they argue over a trick gone bad, Brian walks out on the family and Peter replaces him with a cat. Brian struggles to assert his civil rights and soon ends up at the pound. Luckily, Peter is able to bail him out by bribing the judge.

Global Dynamics goes into lockdown to protect itself from the now airborne metal-eating bacteria. Stuck inside GD, Sheriff Carter and Stark must work together to save both the town and Kevin, Alison's son.