Evidence for the potential utility of GABA B antagonists has been assembled from a variety of sources, including clinical experience with the GABA B agonist baclofen, murine genetic GABA B knock-outs, rodent studies of GABA B receptor expression and function following treatment with antidepressant therapies, animal models of depression, and some functional and post mortem data from human subjects. Definitive testing of GABA B antagonists in depression, however, still awaits the development of potent, selective and brain-penetrant compounds for human testing.