Abstract Developments in the pharmacologic treatment of depression during the past 4 decades have significantly affected the management of depression in the clinical setting. Controlled trials have clearly established the antidepressant activity of tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), classes of drugs that have been available for more than 30 years. Newer agents include the selective serotonin reuptake inhibitors (SSRIs). It has not been possible to identify specific populations of patients with low serotonin depression particularly responsive to these agents. Recent evidence, however, indicates that the SSRIs are more effective than noradrenergic agents for the treatment of obsessive-compulsive disorder and anxiety disorders. Monoamine oxidase A selective, rapidly reversible MAOIs are another recent development. Clinical experience to date with these drugs suggests that their effects are not limited to atypical depression, but extend across the range of depressive disorders. Recently, the focus has shifted to longer-term treatment and to problems in the delivery of available treatments, which often are not used to their maximum benefit.