Clinical thyroid disorders are frequently associated with psychiatric symptomatology, thus supporting a role for thyroid hormones in the biological basis of psychiatric disorders, particularly mood disorders. Despite extensive literature documenting various abnormalities of thyroid function tests in primary major depression, the role of thyroid hormones in the pathophysiology of affective disorders remains to be clarified. In this review, we describe the various abnormalities of thyroid hormone levels reported in primary affective illness. We also review the competing hypothesis to explain the abnormalities of thyroid function observed. Although neither model can fully explain the role of thyroid hormones in depressive illness, they provide working hypotheses for further study. Additional research is required to clarify the regulation of thyroid hormones by mature brain and the role of these hormones in the biological basis of affective illness.