Cardiopulmonary bypass has been demonstrated to produce a state of functional hypothyroidism characterized by low levels of circulating tri-iodothyronine and elevated levels of reverse Tri-iodothyronine. This low tri-iodothyronine state may have significant hemodynamic consequences similar to that seen with chronic hypothyroidism. In a number of experimental models, evidence has accumulated suggesting that tri-iodothyronine supplementation to the ischemically injured heart enhances ventricular contractile performance. Clinically, tri-iodothyronine supplementation after cardiac surgery improves hemodynamics, although the population of patients who might benefit from this unconventional therapy remains unclear. In this article, the rationale and experimental evidence for the use of tri-iodothyronine during cardiac surgery are reviewed.