Naltrexone is an opioid receptor antagonist that has been shown to be effective for maintaining abstinence in alcohol-dependent persons. It is particularly effective in a subset of persons who suffer from high craving, as it reduces craving for alcohol. Family history has been shown to be a predictor of treatment response and, indeed, allelic variation in the mu opioid receptor gene predicts treatment response to naltrexone. The therapeutic effects of naltrexone are mediated by blockade of central mu opioid receptors. The site of action is under investigation but evidence supports a role of mu opioid receptors in the central nucleus of the amygdala, nucleus accumbens, and ventral tegmental area in the therapeutic actions of naltrexone for alcohol dependence. This article reviews the role of the endogenous opioid system in addictive diseases, especially alcoholism and discusses the pharmacological basis for the use of naltrexone in the treatment of alcohol dependence.