Activation of the sympathetic nervous system is an important factor in the genesis of ventricular arrhythmias in patients with impaired ventricular function. Such patients have an appropriate substrate that is capable of generating rhythm abnormalities, which may be related to enhanced automaticity, triggered automaticity, and reentrant mechanisms; all three mechanisms are markedly potentiated by the action of catecholamines. Additionally, the sympathetic nervous system can provoke the development of hypokalemia and ischemia (which can independently lead to the occurrence of rhythm disturbances), and catecholamines may negate the beneficial electrophysiological actions of antiarrhythmic drugs. A substantial amount of experimental data implicates the sympathetic nervous system as a potent stimulus for ventricular tachyarrhythmias and sudden cardiac death, especially in the setting of myocardial ischemia. Two important mechanisms that have been identified include 1) enhanced sympathetic outflow from the central nervous system and 2) nonuniform myocardial denervation resulting in beta-receptor up-regulation and catecholamine hypersensitivity in the infarct zone. Disruption of sympathetic neural innervation of the heart and the use of beta-blocking agents may reduce the occurrence of sudden death and improve survival in animal models of arrhythmias and in some subsets of patients, including those with the long QT syndrome, a recent myocardial infarction, and perhaps those with a cardiomyopathy. The mechanism of this beneficial effect remains to be defined.