The relation between thyroid function and depression has long been recognized. Patients with thyroid disorders are more prone to develop depressive symptoms and conversely depression may be accompanied by various subtle thyroid abnormalities. Traditionally, the most commonly documented abnormalities are elevated T4 levels, low T3, elevated rT3, a blunted TSH response to TRH, positive antithyroid antibodies, and elevated CSF TRH concentrations. In addition, thyroid hormone supplements appear to accelerate and enhance the clinical response to antidepressant drugs. However, the mechanisms underlying the interaction between thyroid function and depression remain to be further clarified. Recently, advances in biochemical, genetic, and neuroimaging fields have provided new insights into the thyroid-depression relationship.