The multiple manifestations of depression may mimic those associated with many physical illnesses, leading to delay in diagnosis. The consequences of depression are disability, suffering, and sometimes death by suicide. Antidepressant drugs have greatly improved the prognosis for the depressed patient. Tricyclics are the drugs of first choice, with monoamine oxidase inhibitors playing a secondary role except in special instances. Drugs can be used along with electroconvulsive therapy when treatment is urgent. Differences in the pharmacologic effects of tricyclics may affect their choice for individual patients. Monitoring of plasma concentrations of tricyclics may uncover some sources of drug failure, such as altered drug kinetics in an individual patient or noncompliance with treatment. Side-effects of antidepressant drugs are numerous; most represent extensions of known pharmacologic actions. Overdoses produce severe intoxications that require expert and assiduous management.