This article reviews the use of opioid antagonists in the pharmacologic treatment of alcohol dependence. The rationale for using the opioid antagonists naltrexone and nalmefene to prevent relapse in alcohol-dependent subjects is discussed by reviewing past and current clinical trials. The role of psychotherapies, particularly coping skills therapy, in combination with opioid antagonists is highlighted in the presentations of the clinical data. Finally, future research directions for opioid antagonists are discussed.