&NA;This paper reviews the neuroanatomy and neuropharmacology of the central serotonergic system. Clinical evidence implicating altered serotonergic function in patients with affective disorders is summarized, as are the attempts to uncover central serotonergic dysfunction in these patients using pharmacological challenges. The authors conclude that the function of the brain serotonergic system in patients with affective disorders is relatively unexplored and would be a fruitful area of study for both the clinician and researcher.