Publisher Summary Heart failure (HF) is a major public health problem in western countries. Experimental and clinical findings strongly support the concept that iodine and thyroid hormone (TH) have a fundamental role in cardiovascular homeostasis. Iodine is an essential component of the TH molecule. Biologically active triiodothyronine (T3) modulates cardiac contractility, heart rate, diastolic function and systemic vascular resistance through genomic- and nongenomic-mediated effects. The importance of THs in maintaining cardiovascular homeostasis is also deducible from data showing that mild forms of primary thyroid dysfunction, i.e., subclinical hypothyroidism and subclinical hyperthyroidism, significantly alter cardiovascular function and negatively affect the prognosis of cardiac patients. Dietary iodine deficiency still remains the leading cause of congenital hypothyroidism; hypothyroidism is also more prevalent and marked in adult persons consuming excessive amounts of iodine. Experimental studies in humans showed that a low thyroid state may alter cardiac histology, cardiomyocyte morphology and cardiac gene expression of structural and functional key proteins. Transformation from the fetal to the mature heart coincides with the rapid surge of TSH and T3 levels after birth. The re-activation of the fetal gene program observed during HF in adult life appears to be reversible when a normal thyroid hormone profile is restored. In patients with HF and low-T3 state, who received intravenous L-T3, cardiac output improved rapidly and systemic vascular resistance decreased; heart rate, BP and metabolic demand were unchanged.