The film begins in Mexico, where police officer Javier Rodriguez Rodriguez (Del Toro) and his partner, Manolo, stop a drug transport and arrest the couriers. Their arrest is interrupted by General Salazar (Milian), a high-ranking Mexican official. The general decides to hire Javier and instructs him to locate and apprehend Frankie Flowers (Collins, Jr.) a notorious hit man for the Tijuana Obregón Drug Cartel.

Meanwhile, Robert Wakefield (Douglas), a conservative Ohio Judge, is appointed to be head of the President’s Office of National Drug Control, taking the title of Drug Czar. Wakefield is warned by his predecessor and several influential politicians that the war on drugs is unwinnable. Unbeknownst to Wakefield, his honor student daughter, Caroline (Christensen) is using cocaine and falls victim to drug addiction when she is introduced to freebase cocaine by her boyfriend, Seth (Grace). She and Seth are arrested when another student at her high school overdoses on drugs and they try to dump him anonymously at a nearby hospital. Robert finds out that his wife Barbara (Irving) has known about their daughter’s involvement with drugs for over six months.