Major depression is often a chronic and recurrent disorder. Findings from a landmark study, the Pittsburgh Study of Maintenance Therapies in Recurrent Depression, demonstrate that full doses of antidepressants prevent recurrent depression and that maintenance therapy lasting at least 5 years may be required for patients with severely recurrent disease. In addition, psychotherapy is a useful adjunct to antidepressant maintenance therapy in prolonging the duration between recurrent episodes. The currently accepted approach to preventing recurrent depression is to treat the acute episode to full remission and follow up by maintaining the patient on the full, acute dose used to achieve the initial response. The selective serotonin reuptake inhibitors (SSRIs) have been studied in recurrent depression and are rational choices for initial maintenance therapy because of demonstrated efficacy, safety, and tolerance during long-term therapy.