Sertraline is a highly selective serotonin re-uptake inhibitor (SSRI) whose efficacy in depression has been established in a number of large placebo-controlled studies in patients with moderate to severe major depressive episodes (DSM-III). This antidepressant efficacy appears to be significantly more effective than placebo and imipramine and at least of the same order as that of the reference tricyclic antidepressants (TCAs) amitriptyline, clomipramine and dothiepin. More recently, two double-blind parallel group studies have demonstrated comparable efficacy to another SSRI, fluoxetine. Sertraline has demonstrated efficacy in the long-term maintenance and prophylaxis of depression and is one of the few SSRIs currently indicated for the prevention of relapse and recurrence of depression. Fixed dose studies have confirmed the efficacy and optimal tolerability of the minimum 50 mg dose. The efficacy of sertraline, demonstrated across a broad spectrum of depression, and its consistently improved tolerability and safety profile over the TCAs, confirm its potential as a first- line treatment for acute and recurrent episodes of depression.