1. Somatostatin is a peptide that is widely and discretely distributed throughout the central nervous system. 2. Its relevance to neuropsychiatric disorders is suggested both by the existence of disease-related alterations in somatostatin content in brain and cerebrospinal fluid as well as by the manifold neuroregulatory capabilities of somatostatin and related peptides. 3. This article will summarize the central nervous system effects of somatostatin, identify those neuropsychiatric disorders that are characterized by changes in somatostatin, and review the evidence for and potential significance of decreases in cerebrospinal fluid somatostatin in depression.