Several natural lipids have emerged as candidate modulators of central nervous system (CNS) functions. Fatty acid amides and their coupled signaling pathways are known to regulate several physiological and behavioral processes. Recent studies from our laboratory and others also have implicated endogenous marijuana-like brain constituents, endocannabinoids (ECs), and cannabinoid-1 (CB1) receptors in the neural circuitry that mediate drug addiction and neuropsychiatric disorders. Neuroadaptation to chronic ethanol (EtOH) has been shown to involve changes in the EC system. These changes include alterations in the synthesis of EC, their precursors, as well as density and coupling efficacy of CB1 receptors. The evidence for the participation of the EC system in the pathophysiology of various neuropsychiatric disorders is just beginning to evolve. It is of great interest to explore the components of EC system in different areas of the CNS for further understanding of its role in health and disease. This article presents a comprehensive overview of the currently available literature pertaining to the role of the EC system in alcoholism, schizophrenia, depression and/or suicide.