This article presents information needed by the clinician to diagnose and treat acute depression. The emphasis is on the pharmacologic treatment of depression. Both clinical and preclinical pharmacology of antidepressants are reviewed. The data presented will help the clinician make a rational choice of antidepressant for his or her patient. In particular, these data will help the clinician avoid or minimize certain adverse effects and drug-drug interactions. Guidelines for treating depression as well as strategies for treating the refractory patient are presented.