The term sicario goes back to Roman Palestine, where a Jewish sect, the Sicarii, used concealed daggers (sicae) in their murders of Romans and their supporters. In modern language, a sicario is a professional killer or a hit man.

In an anonymous motel room on the U.S./Mexico border, a Ciudad Juárez hitman speaks. He has killed hundreds of people and is an expert in torture and kidnapping. He was simultaneously on the payroll of the Mexican drug cartels and a commander of the Chihuahua State Police. There is currently a $250,000 contract on his life and he lives as a fugitive, though he has never been charged with a crime in any country. With his face obscured by a black mesh hood, he tells his story to the camera inside the very motel room he once used to hold and torture kidnapped victims. Aided only by a magic marker and notepad, which he uses to illustrate and diagram his words, the sicario describes, in astounding detail, his life of crime, murder, abduction and torture.

"A minimalist study in maximum violence, Gianfranco Rosi's El Sicario Room 164 offers viewers the rare chance to meet a Mexican narco hitman and to live to tell the tale." —Variety

"El Sicario, Room 164, one of the most revealing and shocking documentaries ever made about the drug trade, is mostly a series of fixed shots of a masked man talking to a camera. The sicario's story is a familiar, eerily three-act rise-and-fall crime saga: A young poor child is seduced by a Mexican's cartel's vast power and gradually evolves from performing petty errands and crimes to kidnapping and torturing people for maddeningly vague reasons. Eventually tiring of the lifestyle's accompanying drug abuse and alcoholism, the assassin becomes a pariah in danger of winding up on the wrong end of a gun himself. There are haunting, inventive touches that quietly speak to the matter-of-factness of his dehumanization: The former killer sketches accompanying images on a pad while talking, and he occasionally rises from his chair to pantomime some of his more outrageous acts. These simple gestures, which speak of the effectiveness of elegantly pared filmmaking, suggest a truth, and a disturbing empathy, that more enraged, self-righteous documentaries rarely manage: the terrifyingly casual roots of evil." —Chuck Bowen, Slant Magazine