The Vampire's Assistant, based on the popular series of books by Darren Shan called The Saga of Darren Shan, is a fantasy-adventure about a teenager who unknowingly breaks a 100-year-old truce between two warring factions of vampires, a peaceful group called the Vampire Clan who don't kill their victims, and a group of stereotypical bloodsucking killers called the Vampaneze. Pulled into a fantastic life of misunderstood sideshow freaks and grotesque creatures of the night, one teen will vanish from the safety of a boring existence and fulfill his destiny in a place drawn from nightmares.
Typical 16-year-old Darren (Chris Massoglia) hung out with his best friend Steve (Josh Hutcherson), got decent grades, and usually stayed out of trouble. But when he and Steve stumble upon a traveling freak show, Steve recognizes one of the performers as a vampire. After the police shut down the show, Darren and Steve get separated. Steve goes to the vampire Larten Crepsley (John C. Reilly) and tries to convince him to make Steve into a vampire. Darren went to steal Crepsley's poisonous spider Madam Octa, and overhears the conversation between Crepsley and Steve. Crepsley says Steve has bad blood and refuses to turn him into a vampire. Steve swears to kill Crepsley and leaves.
When Crepsley realizes that Madam Octa has been stolen, Darren runs away as fast as he can until he runs into a limo. He is told to get inside and there he meets Desmond Tiny (Michael Cerveris) and Murlough (Ray Stevenson). They drop him off at his house where he sneaks back into his room.
The next day at school, Darren has Madam Octa in his locker and Steve sees him talking to her. Darren reveals he overheard the conversation between Steve and Crepsley. As Steve tries to take a look at Madam Octa, she escapes and bites him. Darren goes to Crepsley to ask for the antidote. Crepsley agrees to under the condition that Darren become his assistant as a half vampire. Darren agrees reluctantly and Crepsley bloods him. They go to the hospital where Crepsley administers the antidote. Darren then sounds the alarm forcing Crepsley to leave without him. However the vampire part of Darren soon begin too be to much for him to handle. After Darren nearly feeds on his sister he agrees to leave with Crepsley. He fakes his own death and a funeral is held for him. During the wake Steve notices the scars on his fingertips from when Crepsley converted him into one of his own kind.
Crepsley then digs up Darren's grave when they are attacked by Murlough. Murlough wants to capture Darren and bring him to Tiny. Crepsley eventually manages to lose Murlough and return to the Cirque. Darren meets and becomes friends with Evra Von (Patrick Fugit) the snake boy and Rebecca (Jessica Carlson), a girl with a monkey tail, and the three quickly become friends from the work they do together. As Steve is contemplating suicide, Mr. Tiny stops him and offers him a chance to become a Vampaneze like Murlough. Tiny has several Vampaneze go to the Cirque to kidnap Darren. As Darren hasn't fed yet he doesn't have any powers and is forced to run while the rest of the Cirque tries to stop them. In the end they kidnap Rebecca and have Evra tell Darren to go home.
Steve walks into the Shan house to ask them to adopt him which they refuse. He then has Murlough capture them. Darren arrives too late to save his family and sees the flier for Cirque Du Freak. Crepsley learns where Darren went and goes after him. Darren arrives at the theater he and Steve saw Cirque Du Freak were Murlough and Steve are waiting for him. Steve offers Darren a chance to join them. If he kills Rebecca, Steve will let his family go. Darren refuses and tries to fight them but is easily overpowered from not drinking any blood.
Crepsley arrives and fights Murlough. Rebecca uses her tail to free herself while Mr. Tiny watches from the balcony. Steve helps Murlough against Crepsley while Rebecca offers Darren some of her blood. He reluctantly agrees and help Crepsley against Steve and Murlough. Crepsley kills Murlough and then Steve and Darren fight. Tiny stops them before turning Murlough into a Little Person. Tiny, Steve and Murlough then leave.
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