Combining pharmacotherapy with psychosocial and behavioral interventions has helped improve the treatment of alcohol dependence. However, the clinical use of effective medications, such as naltrexone, is limited by poor adherence to a daily oral regimen. Recently, a once monthly extended-release injectable formulation of naltrexone (Vivitrol, Alkermes, Inc.) became the first FDA-approved long-acting formulation of naltrexone for alcohol dependence. Compared with the oral preparation, extended-release naltrexone shows reduced peaks and minimal fluctuations in plasma levels that may possibly lead to a more benign adverse-event profile. The administration of long-acting naltrexone in conjunction with psychosocial support has been associated with significant improvement in drinking outcome measures, especially among patients who are abstinent entering treatment. Additional studies are warranted to increase the knowledge on the clinical applications of long-acting naltrexone in other addictive disorders and to compare extended-release naltrexone with other long-acting formulations that are in development. The clinical availability of extended-release naltrexone has the potential to enhance treatment outcomes for alcohol and other drug dependence disorders.