Major depression is a common disorder. Historically, tricyclic antidepressants have been the standard pharmacologic agents in the treatment of this disorder. Unfortunately, the occurrence of significant side effects has limited the use of these drugs. In the past decade, however, antidepressants that are pharmacologically distinct from the tricyclics have been introduced. These newer drugs are tolerated better than the tricyclics and have been reported to have similar efficacy. Thus, because these newer agents provide effective, well-tolerated treatment of mild to moderate depression, they are now generally preferred to the tricyclic antidepressants, despite their greater cost.