The use of antidepressant pharmacotherapy to treat patients with co-occurring depression and alcohol dependence is controversial. There is a stigma attached to giving medications to alcohol-dependent persons. Also, empirical evidence is sparse and inconsistent, which discourages the use of antidepressants in these patients. Historically, it has been a challenge to accurately diagnose a depressive disorder in the presence of alcohol dependence. In addition, early clinical studies were fraught with methodological problems; however, improved diagnostic assessments are now available, and in the last decade, results from well-controlled trials appear to support the use of antidepressants in this patient population in the specific role of relieving depressive symptoms. The majority of these trials also demonstrate that antidepressants have relatively little impact on reducing heavy drinking in this patient population, even though the medications reduce depressive symptoms. Newer approaches to treating patients with co-occurring depression and alcohol dependence suggest adding to the antidepressant a pharmacotherapy that directly impacts drinking. The findings from this review better define the action of antidepressants in patients with co-occurring depression and alcohol dependence as specific to reducing depressive symptoms, and these medications and their action on mood have little impact on treating the co-occurring alcohol dependence.