Intense exercise requires a significant increase in cardiac output in order to meet the needs of the skeletal muscles for oxygenated blood. In order to improve cardiac performance, the autonomic nervous system increases sympathetic tone primarily through release of norepinephrine from postganglionic receptors to stimulate the β-adrenergic receptors of the nodal and muscle tissue of the heart. This event initiates a signaling cascade focused on increasing the amount of calcium available to the contractile myofilaments in the cardiac cell. Failure of the myocytes to counterbalance the increase in inward ion flow or adequately sequester cytosolic calcium during diastole leads to potentially catastrophic electrical instability. In this review, the relationship between the cellular events initiated by exercise and the induction of arrhythmias associated with the long QT, Brugada, and Wolff-Parkinson-White syndromes; catecholaminergic polymorphic ventricular tachycardia; and the heritable cardiomyopathies are explored.