In the past decade, 8 new antidepressants were approved for use in the United States by the US Food and Drug Administration. Six of these have been marketed in the United States since 1992. Two additional drugs marketed outside the United States as antidepressants have been approved in this country for obsessive-compulsive disorder. Together with the conventional antidepressants, the new ones, and the 2 drugs available off-label, the physician can choose from a list of 22 compounds to treat the depressed patient. This article reviews theories about the mechanisms of action of antidepressants and the basic pharmacology of the newer-generation drugs in relation to the older compounds. We hope this information is of use to the clinician in treating acute depression with pharmacologic agents.