Emerging evidence suggests that the amino acid neurotransmitter systems are associated with the pathophysiology and treatment of mood disorders. Recent advances in the areas of molecular neurobiology, pharmacology, and magnetic resonance spectroscopy (MRS) now provide better tools to probe the function of the amino acid neurotransmitter systems and are affording us the opportunity to better investigate the relationship of these systems to mood disorders. Here we review the available literature in the field and suggest a possible pathophysiological model that may account for the many of the findings.