Antidepressant drugs are effective for treating moderate to severe depression associated with psychomotor and physiological changes such as loss of appetite and sleep disturbance; improvement in sleep is usually the first benefit of therapy. They are also effective for dysthymia (lower grade chronic depression). Antidepressant drugs are not generally effective in mild depression, and cognitive behavioral therapy should be considered initially; however, a trial of antidepressant therapy may be considered in cases refractory to psychological treatments or those associated with psychosocial or medical problems. Drug treatment of mild depression may also be considered in patients with a history of moderate or severe depression. There is little to choose between the different classes of antidepressants in terms of efficacy, so choice should be based on the individual patient’s requirements, including the presence of concomitant disease, existing therapy, suicide risk, and previous response to antidepressant therapy. Since there may be an interval of 2 weeks before the antidepressant action takes place, electroconvulsive treatment may be required in severe depression when delay is hazardous or intolerable. Patients should be reviewed every 1–2 weeks at the start of antidepressant treatment. Treatment should be continued for at least 4 weeks (6 weeks in the elderly) before considering whether to switch antidepressant due to lack of efficacy. In cases of partial response, continue for a further 2 weeks (elderly patients may take longer to respond). Following remission, antidepressant treatment should be continued at the same dose for at least 6 months (about 12 months in the elderly). Patients with a history of recurrent depression should continue to receive maintenance treatment for at least 2 years.