Long-term treatment with antidepressants is now an accepted strategy in the management of depression. The demonstration of efficacy in this setting requires specific placebo-controlled trials of patients with recurrent depression studied after an adequate period of euthymia and for a long period of follow-up. This review examines the evidence for the prophylactic efficacy of antidepressant therapy with particular emphasis on the selective serotonin reuptake inhibitor, paroxetine.