Alcohol interacts with many neurotransmitter systems, including the endogenous opioid peptide system, which influences the mesolimbic dopamine system and is believed to be central to drug-induced reward. These observations emphasize the need to further characterize the alcohol-opioid system link. Two important clinical studies have shown that treatment with the systemically active opioid antagonist naltrexone reduced the frequency as well as the severity of an alcohol slip (i.e., prevented relapse) among alcohol-dependent subjects who were enrolled in outpatient alcoholism treatment programs. Multiple interactions between opioid peptides and various receptors complicate our understanding of these brain mechanisms. Two possible therapeutic approaches to alcohol addiction include interfering with alcohol-induced reward and reducing sensitivity to alcohol by administering drugs that selectively block or reinforce only one selected opioid system.