Before the advent of the pharmacologic treatment of depression, there were theories about the biological basis of affective disorders. However, today's theories are derived largely from known pharmacologic effects of antidepressants. These effects, derived from neurochemical studies with laboratory animals, have implicated catecholamines and serotonin in depression. Although most antidepressant drugs in use today have been available for decades, their mechanism of action in treating depression has not been established. In addition, theories about the biological causes of depression have not been proven. Nevertheless, the rich pharmacology for antidepressant drugs involving blockade of neuronal uptake systems for some biogenic amines and blockade of many receptors for neurotransmitters can explain some of their adverse effects and certain interactions with other drugs.