Pharmacotherapy, in conjunction with psychosocial interventions, is emerging as a valuable tool for alcohol dependence treatment. Currently, four agents are approved by the Food and Drug Administration for this purpose: disulfiram, acamprosate, oral naltrexone, and the once-monthly injectable, extended-release naltrexone. All four agents have demonstrated some ability to reduce drinking and/or increase time spent abstinent, but results have not always been consistent. Except disulfiram, which has an aversive mechanism of action, effective pharmacotherapies for alcohol dependence are thought to work by blocking the rewards of alcohol or stabilizing systems dysregulated by chronic alcohol intake. Topiramate and baclofen have also demonstrated some efficacy in treating alcohol dependence. The efficacies of many of these regimens are modest and are limited by patient nonadherence to treatment and disease heterogeneity. Pharmacotherapeutic effectiveness could be enhanced through increased knowledge of the pathophysiology of alcohol dependence, through the identification of predictors of response to specific medications, and by modalities that improve medication adherence. (c) 2009 Published by Elsevier Inc.