Appreciation has grown for the impact of the autonomic nervous system on the development of clinical cardiac arrhythmias. Antiarrhythmic medications work to significantly prolong cardiac repolarization and slow conduction. The question has arisen whether these pharmacologic actions of antiarrhythmic drugs can be modulated by alterations in the sympathetic nervous system. This article examines the data pertaining to modulation of the class I and class III effects of antiarrhythmic drugs during beta-adrenergic stimulation, the body's natural response to stress. The actions of several antiarrhythmic drugs can be fully reversed during beta-adrenergic sympathetic stimulation. Overall, the data suggest that pure class III drugs are the most susceptible to reversal of their effects on refractoriness, followed by class IA agents, amiodarone (which has partial resistance), and d,l-sotalol (which is highly resistant to reversal). Whereas retrospective analyses of a number of trials suggest that sympathetic-stimulation-induced reversal of the electrophysiologic effects of certain antiarrhythmic drugs can decrease their clinical efficacy, prospective trials examining this issue are needed. At the current time it appears reasonable to administer beta blockers to patients receiving antiarrhythmic agents that do not have intrinsic antiadrenergic effects.