γ-Hydroxybutyric acid (GHB) is unfamiliar to many physicians in the United States but enjoys clinical use elsewhere for applications in resuscitation, anesthesia, and addiction therapy. Use within the United States is restricted to Food and Drug Administration– approved clinical trials for treatment of narcolepsy. Recently illicit use of GHB has emerged within the United States where it is distributed for purported euphoric and “fat-burning” metabolic effects. Clinical effects can be severe, progressing rapidly to respiratory arrest and death. We provide an updated comprehensive review of the literature with particular emphasis on toxicology, including GHB pharmacodynamics, clinical effects, and suggestions for overdose management. Recommended management of acute GHB intoxication includes prevention of aspiration, use of atropine for persistent symptomatic bradycardia, consideration of neostigmine as a reversal agent, and treatment for coingested substances. Emergency physicians are urged to become familiar with GHB because of its potential for severe morbidity, as well as its potential use as a future resuscitative agent. [Li J, Stokes SA, Woeckener A: A tale of novel intoxication: A review of the effects of γ-hydroxybutyric acid with recommendations for management. Ann Emerg Med June 1998;31:729-736.]