With Hannibal behind bars, a new threat arises in Francis Dolarhyde, and Jack is once again forced to turn to Will for help.
It takes one look at the William Blake painting "The Great Red Dragon and the Woman Clothed with the Sun" for Francis Dolarhyde to become the Red Dragon. He gets the creature tattooed on his backside and purchases a set of fake teeth perfect for biting. In his home, he frames a replica of the painting and worships it. But at the same time the Red Dragon is born, Hannibal is caged. He is moved into a room at the Baltimore State Hospital for the Criminally Insane, complete with drawing and dining tables and a wall of glass that separates him from visitors.
Three years after his surrender, Hannibal still resides there, having pled insanity and avoided the needle, according to Alana. When she, now the director of the hospital, visits with Hannibal, he reiterates his promise to kill her. Sometime after, Hannibal gets another visitor, Dr. Chilton. They sit on the same side of the glass, at Hannibal's dining table, and enjoy the Italian dessert sanguinaccio dolce while Chilton attempts to gauge Hannibal's feelings about the new serial killer in town. The Red Dragon, whom the press has taken to calling the Tooth Fairy, murders entire families in their homes. Hannibal tells Chilton he doubts the Tooth Fairy enjoys being called that.
When Alana walks into her office, Chilton is sitting at her desk. She reveals that Hannibal wrote a piece for the American Journal of Psychiatry that contradicts everything Chilton described in his book about him. Chilton is not overly concerned with being discredited, though Alana believes he could be. What's more pressing to him is that the Red Dragon could inspire Hannibal to get up to his old tricks.
While watching a film on a projector, Francis' head begins pounding, and the Red Dragon takes over. He cuts articles written about him from a newspaper and hastily glues them into a scrapbook. At the same time, Hannibal, much more precisely, does the same. Hannibal's fascination with the Red Dragon turns out to be reciprocated. Francis' scrapbook contains clippings of articles about Hannibal and Will, too. But just as Hannibal predicted, the Tooth Fairy moniker makes Francis upset. He crosses it out with a black marker.
With two families now having been slaughtered, Jack has no choice but to pay Will a visit. He asks Will how much he knows about the Tooth Fairy and if he's ever considered giving him a call. Will emphatically says no. He doesn't think that way anymore. Jack pulls out photos of the crime scenes to try to sway Will and shares that he believes the killer is in phase with the moon, which means they have little more than three weeks before he strikes again. Before Will can respond, Molly, his wife, and Walter, her son, arrive and cut the conversation short.
While picking out firewood, Molly confides in Will that Jack stopped by to see her at the shop first and that she purposely gave him wrong directions to the cabin. She asks Will if he's going to help him. Will answers that helping Jack is bad for him. Over dinner, Jack marvels at the life Will has made for himself with his family and growing brood of strays. When Walter takes the dogs outside for a walk, Will goes with him. Molly turns to Jack; she knows Jack will take Will with him no matter what. That night, Will awakes in the middle of the night and pulls out an envelope from a dresser drawer. He opens it by the fire and reads a letter from Hannibal. Along with the letter is the clipping about the Tooth Fairy Hannibal set aside. Hannibal warns Will that Jack will come knocking on his door soon and that he shouldn't go with him. Without a second thought, Will tosses the letter into the fire.
Will visits the home of the second murdered family, the Leeds. He explores the first floor, discovering a half-eaten piece of cheese in the fridge. Following a blood trail upstairs, Will enters the kids' room, where blood splatter on the wall and the floor helps him envision how the two boys were killed. In the hallway, a mirror is smashed and a large pool of blood indicates where Mr. Leeds was killed. Entering the master bedroom, Will sees one wall and the bed are covered in blood as well. He flips through the case file and forces himself to once again enter a killer's mind. It comes back to him like riding a bike.
Retracing the killer's steps, Will learns that the Red Dragon slit Mr. Leeds' throat then shot Mrs. Leeds. The bullet didn't kill her, so he later strangled her. When the killer saw Mr. Leeds trying to make his way to the door, he realized he was trying to protect the children. After throwing Mr. Leeds to the ground, the Red Dragon shot one boy while he slept in bed and pulled out the other, who was trying to hide, from under the bed and shot him on the floor. Returning to the hallway, he discovered Mr. Leeds crawling along the floor. The Red Dragon next smashed mirrors in the home and placed the shards on the bodies' eyes and mouths. He propped up the family in the master bedroom like a tableau before returning the bodies to the places where they were killed. Talcum powder on Mrs. Leeds' body shows Will that before the killer left, he removed his glove to touch her body.
Jimmy Price and Brian Zeller are brought in to inspect Mrs. Leeds' body. Brian creates a replica of the Red Dragon's teeth from bite marks he left on his female victims and the piece of cheese. Jimmy discovers a partial print on Mrs. Leeds' hemorrhaged eyeball and smudged prints on the shard of glass placed in her labia. Will explains that the killer polished the shards after placing them so he could see himself reflected in them. Despite how naturally profiling comes to him, Will is no happier on the job than he was working alongside Hannibal. He pours himself a drink and calls Molly that night. She doesn't answer.
The next day, Will speaks with Jack and says there's one other thing he could be doing to help. Jack knows where this is headed and isn't pleased, but Will sees no other option. Later that day, he visits Hannibal.