After a car crash that kills the man behind the wheel, Stacy (Adrien Brody), Walker (John Malkovich) and Gage (Rory Culkin) find themselves in a car outside a warehouse. They go inside to try and find a different car to leave in so they are safe. They head inside and find themselves wandering in the warehouse before finding a locker room. Inside the locker room, Gage goes through a series of lockers and finds drugs, medical supplies, and testosterone. He then finds a dead body, the dog's handler, and a monster Presa Canario who lives in this dog fighting warehouse. Meanwhile, interspersed flashbacks occur of the dog from the dog fighting ring and Blue (Antonio Banderas) who has abused the dog in order to make it fight. Sitting and waiting while trapped by the Mastiff, Stacy tells Walker the story of how he became a dog lover.Gage is revealed to be in the locker room trying to get the drugs, where he injects heroin. There is a brief chase when Gage asks to be let back in with his drugs and the animal attacks. Walker is injured, as is Gage. Then they find out about the dog fighting that was going on there the night before, and Gage tells the story of his first dog. Gage then overdoses and dies. Stacy goes to find the keys to a vehicle in order to get Walker out of there with his injury, after Walker rejects Stacy calling an ambulance.Stacy retrieves the keys and after being chased by the dog, Stacy hides in a piano from the dog. The dog realizes that Stacy is in the piano and charges, but becomes trapped under the piano. Stacy debates leaving, but instead lifts the piano off the dog, who then leaves Stacy intact. Stacy fetches Walker and takes him to the vehicle, where Blue pulls up in a car and shoots Walker.Stacy runs through the warehouse to escape Blue who keeps shooting at him, and then falls backwards to escape Blue. They end up in the dog fighting ring where Blue does an evil monologue before the dog shows up and recognizes both Blue, his evil owner who abused him, and Stacy, who saved him from a piano. Blue aims to shoot the dog, but the dog attacks him before being shot, and is mortally wounded, but not before killing Blue. Stacy pets the dog and tells him that it's alright. Stacy is then seen walking across a beach with a puppy.The movie is dedicated to Molly, the dog, my teacher, my friend.