Mitchell has trouble restraining his blood lust, Annie must deal with her past, and George finds that he no longer has a safe place to transform when the hospital renovates the basement storage room. A former girlfriend of Mitchell's, turned into a vampire by him, comes to see him and she has vengeance on her mind.

George meets a homeless werewolf, Tully, a rogue who offers George advice on dating women and teaches George how to deal with his transformations. After Tully tries to sexually assault Annie, Mitchell wants him thrown out of the flat, but George defies him and backs Tully, until Tully tells him how George was turned into a werewolf.

Annie meets Gilbert, a ghost from the 1980s, who shows her her own headstone. Her subsequent exploration of why she has remained on Earth after her death results in her discovering that she was actually murdered by Owen, throwing her emotions into conflict. After Lauren sends Mitchell a DVD of her murdering a man, Mitchell tries to help Lauren give up killing and bring her back to the person she was. George struggles to build a relationship with Nina, unsure of how much he should tell her. Gilbert expresses his love for Annie, and is then permitted to "cross over" to Death through a supernatural doorway. From this, Annie learns that until she fulfills the one thing keeping her Earth-bound, she will never be permitted to cross-over.

Mitchell makes friends with a neighbor's son being bullied by classmates, but a misunderstanding with the mother results in an angry mob attacking the house. The boy runs away and is hit by a car, and it is up to Mitchell to save him. Meanwhile, Nina visits the vandalized house and thinks George is pushing her away because he is a pervert, and Annie starts exhibiting some mental problems as she tries to accept the changes in her existence.

Mitchell believes vampirism can save lives, and returns to the vampires. He finds recruits amongst the terminally ill that come to the hospital he works at, but the vampires aren't telling him their full plan for world conversion. Mitchell reverses himself when he meets an old girlfriend from the 60s, a dance teacher dying from cancer, who teaches him the true meaning of humanity. Annie finally faces Owen about her death and, with Mitchell and George, puts fear into his heart. The doorway comes for Annie and she says her goodbyes, just as Mitchell is stabbed with a stake by Herrick. George frantically dials for an ambulance as Annie must make a decision: cross over to the Afterlife or remain and help her friends.

George and Annie stay with Mitchell in the hospital, worried that he seems to be fading away. Although Mitchell almost dies, his old girlfriend sacrifices herself to save him, allowing him to drain her blood to heal himself. George finally gathers the courage to confront Herrick and defend his friends, but Herrick isn't playing by the rules. Herrick plans to kill George and Nina, and destroy the things keeping Annie Earth-bound, sending her into "nothingness". Mitchell will then have to face the vampire coven alone and be destroyed. Can George keep Nina safe? Can Annie harness her new poltergeist powers in time to defeat the vampires? Will Mitchell succeed in his plan to face Herrick once and for all? In the end, nothing goes as planned for any of them.