Major depressive episodes can be precipitated by a variety of mechanisms, including the administration of medications. We report four cases in which antidepressant medication appeared to exacerbate a major depressive episode to the point of suicide. Subsequent withdrawal of the initially prescribed antidepressant medication led to a partial remission in each case. These case reports point out the possibility of antidepressant medication precipitating suicidal behavior in depressed patients and underscore the need for careful monitoring of symptomatology during the initial weeks of medication prescription in this population.