Major depression afflicts a significant percentage of the population, and optimum therapy is often limited by the poor tolerability and lethality in overdose of the tricyclic antidepressants. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline, and, more recently, paroxetine are viewed as welcome additions to existing therapy. The SSRIs are as effective as the tricyclic antidepressants, but are not associated with their adverse effect profile. Paroxetine in dosages of 20-50 mg/day is as effective as the older classic antidepressants, including amitriptyline, imipramine, and doxepin. It is effective in the elderly and in patients with recurrent, resistant, or severe depression.