The similarities and differences between electroconvulsive therapy (ECT) and antidepressant medications are reviewed with respect to their clinical indications. The implications of the overlap and divergence in their spectra of clinical efficacy are discussed in reference to mechanisms of action. The hypothesis is offered that ECT has multiple mechanisms of action, which differ depending on the clinical syndrome being treated. From this perspective, ECT may share similar mechanisms of action with other agents that are also effective in treating the specific syndrome. Thus, although ECT may result in a plethora of neurobiological effects, depending on the clinical syndrome, specific and differing subsets of neurobiological changes are relevant to therapeutic action.