Thyroid hormones have been considered as viable treatments for patients with mood disorders, particularly those with treatment-resistant illness. Hypothalamic thyrotropin releasing hormone (TRH) has a regulatory effect on the thyroid axis by stimulating thyrotropin (TSH) which, in turn, regulates thyroid hormone synthesis and release. Triiodothyronine (T3) is the most widely and extensively studied thyroid hormone for the treatment of depression. It has been employed as monotherapy, to accelerate antidepressant effect and to augment therapeutic effects in antidepressant non-responders. The majority of the earlier studies employed T3 as it was felt that with its short half-life it would be less likely to cause symptoms of toxicity. It was assumed that thyroxine (T4) would be comparable to T3 in augmentation of antidepressant response as both would enhance thyroid hormone levels. Two of the most commonly employed antidepressant augmentation strategies are the addition of lithium and T3.