Eight patients with refractory mood disorders received chromium supplements and described dramatic improvements in their symptoms and functioning. In several instances, single-blind trials confirmed specificity of response to chromium. Side-effects were rare and mild, and most commonly included enhanced dreaming and mild psychomotor activation. To our knowledge, this is the first case series describing the response to chromium monotherapy. The putative antidepressant effects of chromium could be accounted for by enhancement of insulin utilization and related increases in tryptophan availability in the central nervous system, and/or by chromium's effects on norepinephrine release.