The involvement of the thyroid gland and thyroid hormones is generally believed to be important in the aetiopathogenesis of major depression. Major support comes from studies in which alterations in components of the hypothalamic-pituitary-thyroid (HPT) axis have been documented in patients with primary depression. However, screening thyroid tests are often routine and add little to the diagnostic evaluation. Overt thyroid disease is rare among depressed inpatients. The finding that depression often co-exists with autoimmune subclinical thyroiditis suggests that depression may cause alterations in the immune system, or that in fact it could be an autoimmune disorder itself. The outcome of treatment and the course of depression may be related to thyroid status as well. Augmentation of antidepressant therapy with the co-administration of thyroid hormones (mainly T3) is a well-documented treatment option for refractory depressed patients. Review of the literature suggests that there are no conclusive data on the role of thyroid function in depression. It is clear that depression is not characterised by an overt thyroid dysfunction, but it is also clear that a subgroup of depressed patients may manifest subtle thyroid abnormalities, or an activation of an autoimmune process. There is a strong possibility that the presence of a subtle thyroid dysfunction is a negative prognostic factor for depression and may demand specific therapeutic intervention.