The electrophysiologic basis for the use of amiodarone in the treatment of cardiac arrhythmias is outlined, with reference to studies in isolated cardiac tissues, whole animal, and human studies. Amiodarone appears to have the distinctive property of directly prolonging action potential duration (and hence refractory periods) in nearly all cardiac tissues. Independent of its effects on refractory periods, conduction may also be impaired in the His-Purkinje system, possibly due to depression of phase 0 of the action potential. Sinus node and atrial automaticity, as well as that arising from diseased Purkinje fibers, may be depressed. Normal ventricular escape pacemakers appear relatively unaffected, however. A nonspecific anti-adrenergic action may contribute to its observed effects. These electrophysiological effects are more obvious and predictable after several weeks of oral treatment than after intravenous administration, suggesting a time-dependent mechanism of action. The drug appears well suited to the prevention of enhanced automaticity in the ventricle and re-entry throughout the heart, and its frequent clinical success in a broad spectrum of cardiac arrhythmias attests to this. Unwanted side effects include sinus node depression, His-Purkinje conduction delay or block, and ventricular arrhythmias enhanced by QT prolongation. However, the frequency of clinically significant examples of unwanted arrhythmic effects appears to be acceptably low.