Changes in thyroid status markedly influence cardiac contractile and electrical activity. The predominant route by which triiodothyronine (T3) affects cardiac action is by exerting a direct effect in cardiac myocytes through binding to thyroid hormone nuclear receptor isoforms. In addition, T3 modifies cardiac action by alterations in the vascular system and decreases afterload of the left ventricle by subtle modification related to the sympathetic system. The importance of T3 nuclear receptor function has been further demonstrated by studies in null mutant mice in which thyroid hormone receptor-alpha (TRalpha) and thyroid hormone receptor-beta (TRbeta) or both are deleted. In mice with null mutations of the TRalpha, a markedly decreased heart rate and decreased contractile performance occurs in contrast to mice with deletion of TRbeta that have a normal heart rate and a normal contractile performance under baseline conditions. Thyroid hormone influences on heart rate are exerted by specific ion channel proteins in the sinus node of the left atrium. Some of these ion channels, such as the IF channel, the sodium/calcium exchanger protein, the L-type and T-type calcium channel, and the ryanodine channel are targets for thyroid hormone action. The increased contractile performance induced by T3 is largely mediated by increased expression of the calcium adenosine triphosphatase (ATPase) of the sarcoplasmic reticulum and decreased expression of phospholamban and T3 increases the phosphorylation status of phospholamban. The significant influence that is exerted by thyroid hormone signaling system related to contractile and electrical activity in the heart and the molecular basis for these alterations continues to be clarified.