Presently in the United States, 21 compounds have been approved by the Food and Drug Administration as antidepressants. Two additional drugs marketed outside the United States as antidepressants have been approved for obsessive-compulsive disorder. Nearly one half of all these compounds became available within the past 12 years, whereas the first antidepressant was available more than 40 years ago. After the clinical aspects of depression are introduced in this article, the pharmacology of the newer generation drugs is reviewed in relationship to the older compounds. The information in this review will help clinicians treat acute depression with pharmacological agents.