Thyroxine (T4), a major secretory product of thyroid gland, needs to be converted to 3,5,3'-triiodothyronine (T3) by iodothyronine deiodinases to exert its biological effect. Nonthyroidal illness, also known as low T3 syndrome, is associated with low serum T3 concentrations, which are inversely correlated to the severity of the illness. The patients with nonthyroidal illness do not show compensatory rise in serum TSH concentrations, and sometimes develop low serum T4 and TSH concentrations. It has been postulated that decreased extrathyroidal conversion of T4 to T3 is a responsible mechanism underlying low T3 syndrome. The roles of three types of iodothyronine deiodinases (D1, D2, D3) in the pathophysiology of nonthyroidal illness are discussed.