Octavio (Gael García Bernal) is in love with his brother’s wife Susana (Vanessa Bauche) and dislikes the way she is abused by his brother Ramiro (Marco Pérez). Octavio tries to persuade her to run away with him. Local thug Jarocho, happy after winning in a dog fight, lets his dog loose on some strays and is threatened by a vagrant wielding a machete. Eventually, Jarocho sics his dog on Octavio’s rottweiler, Cofi, but his own dog is killed instead. Made aware of this by his friend Jorge and needing money to start his new life with Susana, Octavio decides to become involved in the dogfighting scene. Jarocho keeps entering new dogs into the fights, only for Cofi to kill them. Octavio makes enough money to flee with Susana, and pays Mauricio, the owner of the dogfighting venue, to get Ramiro beaten up. In revenge, Ramiro steals the money and leaves with Susana. Struggling financially, Octavio accepts a challenge by Jarocho to participate in a private dogfight, with no outside bets. Cofi is about to win, but Jarocho shoots him. In revenge, Octavio stabs Jarocho in the stomach. Pursued by Jarocho’s thugs, Octavio finds himself in a car chase with Jorge and the wounded Cofi. A collision follows; Jorge dies and Octavio is badly injured.
Magazine publisher Daniel (Álvaro Guerrero) leaves his family to live with his lover Valeria (Goya Toledo), a Spanish supermodel. On the day they move in together, Valeria’s leg is severely broken in the car accident and she is unable to continue working as a model. One day, as Valeria is recuperating in Daniel’s apartment, her dog Richie disappears under a broken floorboard and stays there for days. The missing dog triggers serious tension for the couple, causing numerous fights which lead to doubts about their relationship on both sides. Daniel calls his estranged wife to hear her voice, suggesting that he regrets leaving her for Valeria. Trying to rescue the dog, Valeria reinjures her leg; Daniel finds her hours later. Valeria’s new leg injury results in severe arterial thrombosis and eventually gangrene. Her leg is amputated, ending Valeria’s modeling career for good. While she is in the hospital, Daniel rescues Richie from the floorboards. However, Valeria realizes that her life is ruined. She quietly drives her wheelchair through the torn-up lovenest and looks out of the window expecting to see a billboard bearing her likeness, only to find it has been removed.
The vagrant occasionally seen in the previous segments is revealed to be a professional hitman called El Chivo (Emilio Echevarría). Leonardo, a corrupt police commander, recounts that El Chivo is a former private school teacher who was imprisoned after committing terrorist acts for guerilla movements. When he got out, Leonardo started getting him jobs as a hitman. El Chivo tries to make contact with his daughter, Maru, whom he abandoned when he began his guerrilla involvement. Following El Chivo’s wishes, Maru’s mother told her that her father is dead. El Chivo is about to perform a hit on a businessman when the car crash interrupts him. During the chaos at the crash scene, El Chivo steals Octavio’s money and takes the wounded Cofi to his home to nurse it back to health. One day, while El Chivo is away from his warehouse hideout, Cofi kills the other mongrel dogs El Chivo is caring for. Despite initially preparing to kill Cofi, El Chivo figures that the dog does not know any better and that its violence is a reflection of his own life as a hitman. Meanwhile, Ramiro is shot and killed by Leonardo’s plain-clothes bodyguard during an attempted bank robbery.
At Ramiro’s funeral, a seriously injured Octavio sees Susana for the first time since she and Ramiro fled with his money. Despite having been wronged, Octavio tries again to convince Susana to run away with him, but she becomes angry with the fact that Octavio is willing to run away with her after she has just lost a loved one. A few days later, Octavio is shown waiting at the bus station for Susana. She never shows, and Octavio does not get onto the bus. Still grieving for his other dogs, El Chivo learns that his client and his intended victim are half-brothers. He leaves both men alive and chained to separate walls with a pistol within reach between them, their fate left undetermined. El Chivo then breaks into his daughter’s house and leaves her a large bundle of money along with a message on her answering machine explaining what happened to him and why the family was split. Just before El Chivo is to tell his daughter Maru that he loves her, the answering machine stops recording. He then goes to an autoshop, where he sells the client’s SUV. The mechanic asks him the dog’s name, and El Chivo calls him “Negro” (“Black”). After El Chivo receives the money for the car, he and Negro walk away, disappearing into the horizon.