This review assesses the parallel data on the role of gamma‐aminobutyric acid (GABA) in depression and anxiety. We review historical and new data from both animal and human experimentation which have helped define the key role for this transmitter in both these mental pathologies. By exploring the overlap in these conditions in terms of GABAergic neurochemistry, neurogenetics, brain circuitry, and pharmacology, we develop a theory that the two conditions are intrinsically interrelated. The role of GABAergic agents in demonstrating this interrelationship and in pointing the way to future research is discussed. Depression Anxiety 24:495–517, 2007. Published © 2006 Wiley‐Liss, Inc.