Having discovered the existence of supernatural creatures, two mysterious strangers, Professor Jaggat and Kemp, begin to pursue the three housemates with the objective of eliminating them – by any means necessary. After a night out, George and Mitchell are challenged by two married vampires named Ivan and Daisy. They taunt the pair about Herrick’s murder, but Daisy has something else on her mind. George’s relationship with Nina becomes strained after she discovers she is a werewolf, as they seem to avoid the truth. Annie embraces her new-found confidence by applying for a job at the local pub. The wit and honesty of new doctor Lucy captures Mitchell’s attention.

When a bloodied man with suspicious-looking marks on his neck arrives at the hospital, Mitchell realizes that the vampire who helped him go clean has started to kill again. Lucy's curiosity and the vampire coroner's refusal to cover up the killing leads to Mitchell being forced to help his old mentor leave the country in order to preserve the vampires' anonymity. Nina, revolted by George's complicity in the scheme, leaves the house, encountering Kemp in the process. And Annie finds that evil spirits are attempting to force her into crossing over, using Saul as their pawn.

With Annie now invisible to humans again, she resolves to get Hugh reunited with his old girlfriend. George reluctantly agrees, but their plan backfires when George's attempt to be a terrible blind date manages to match up with all of the girl's interests. Meanwhile, Mitchell attempts to convince the local vampires to stop killing, and has to resort to ancient methods of torture in order to be taken seriously. He succeeds, but in doing so is involuntarily crowned the leader of the coven.

George attempts to control his werewolf state by locking himself into a custom-built cage and downing heavy tranquillisers on the night of the full moon. It appears to work, but he later discovers that neutralizing the wolf causes him to become volatile and violent the rest of the month. Annie finds another ghost who helps teach her how to fend off the "agents" attempting to force her to cross over, and begins to learn how to read the auras of both living and supernatural beings. Mitchell starts up a "blood addiction" support group within the coven and persuades Ivan to join up, but when Ivan struggles to control his thirst, Mitchell is forced to compromise.

Mitchell is getting closer to Lucy and she, in turn, is struggling to contain her feelings for Mitchell. Mitchell has only really fallen in love once before and, in a flashback to the Sixties, viewers learn how his relationship with Josie saved him from the excesses of vampiredom. Back in the present with Lucy, it's clear he's struggling to reconcile the difference between human love and vampire lust. Meanwhile, George's relationship with Sam and her daughter, Molly, is going well and George wonders if there might be a chance to make the most of this normal human relationship – could he become Molly's step-father? Annie experiences maternal feelings of her own when she's asked to babysit an unusual child...

Annie befriends a psychic who lost most of his "sixth sense" in an accident and has been unable to communicate with spirits since then. His once awful stage show now serves to help ghosts send their final messages to loved ones – something Annie does as well when her mother attends the show. George's relationship with Sam gets more serious, but when a parent-teacher night falls on a full moon, it forces George to lie about his plans to cover up his secret. Mitchell plans to leave the coven to start a life with Lucy, but unbeknownst to him Lucy orders Kemp to stage an explosion in the funeral parlour, killing most of the vampires.

Mitchell and Daisy, the sole survivors of the explosion, try to get to the bottom of who was responsible. When Mitchell discovers that Lucy was behind it, he goes berserk and vows retaliation, killing Quinn the coroner and, with Daisy massacring passengers in a train carriage (the "Box Tunnel 20"). Nina returns, and offers George a chance at a cure. George initially refuses, but changes his tune when a confusion of time causes him to begin his transformation in public, frightening Molly in the process. Annie also seeks the help of Kemp to cross over, but his methods prove to be quite time-consuming if not utterly pointless.

Mitchell goes on the search for George and Annie, killing anyone who gets in his way. Meanwhile Annie is dragged through "death's door" as a result of Kemp killing the psychic in order to make a doorway. George and Nina then escape with Mitchell to the countryside. Three weeks later Lucy turns up and is killed by Kemp. Just before Kemp goes to kill Nina, George and Mitchell, Annie appears through Lucy's door and pulls Kemp with her back through the door. Annie then appears on a television from the netherworld and explains what is going on. The episode ends with Daisy and Cara (the vampire locked away by Mitchell) participating in a blood ritual in order to resurrect Herrick.