Current guidelines regarding concomitant antidepressants during electroconvulsive therapy (ECT) are inconsistent. Although the American Psychiatric Association Task Force on ECT discouraged combination antidepressant treatment, owing to the minimal evidence for enhanced efficacy and concern about increased adverse effects, combination treatment is recommended and considered routine for many practitioners in the United States and other parts of the world. Considering the increasing levels of treatment resistance among patients referred for ECT and the high relapse rate after acute ECT, the role of concomitant antidepressant pharmacotherapy during ECT should be reevaluated. More research, however, is needed to explore the impact of administering specific antidepressants during acute and maintenance ECT (M-ECT), on antidepressant efficacy and cognitive adverse effects. This will require appropriately controlled studies of ECT medication combinations that include attention to a range of cognitive function measures and clinical response. In addition, the role of combination ECT and psychotropic medication in the treatment of mania and schizophrenia continues to receive attention, particularly in those patients who have shown inadequate responses to psychotropic medication alone. Although there is insufficient evidence to support the routine addition of antipsychotic medications to ECT during the treatment of acute mania, the literature suggests that it is unnecessary to discontinue antipsychotic medication when ECT is added to the treatment of a manic patient that has been unresponsive to pharmacological treatment. Despite the lack of well-controlled studies, the existing literature suggests that combination ECT and antipsychotic treatment is a useful option for patients with schizophrenia who are unresponsive to pharmacological interventions alone, and its adverse effect profile does not seem different from that seen with ECT alone.