The endogenous catecholamines epinephrine and norepinephrine have profound effects on smooth muscle activity, cardiac function, carbohydrate and fat metabolism, hormone secretion, neurotransmitter release, and central nervous system actions. These activities are mediated by GPCRs belonging to two subfamilies, the alpha- and beta-adrenergic receptors. The three members of the beta-adrenergic receptor family, beta1, beta2 and beta3, couple to Gs to increase cAMP upon activation. In the heart, the beta1 receptor constitutes 70-80% of the beta-adrenergic receptors. Activation of cardiac beta-adrenergic receptors, acutely increases heart rate, cardiac output, and cardiac automaticity, and chronically increases cardiac myocyte apoptosis. In failing hearts, the beta1 subtype is downregulated and desenstitized, probably as a result of increased catecholamine levels. As a result, beta-adrenergic receptor antagonists (beta blockers) are effective in the treatment of congestive heart failure and arrhythmia.