The mode of antiarrhythmic action of drugs usually cannot be extrapolated from their electrophysiologic properties despite extensive in vitro and in vivo assessment: in most cases, the mechanism of arrhythmias remains uncertain and cannot be established by clinical evaluation including electrophysiologic study; in specific cases where the arrhythmia substrate is fully described, the exact origin of antiarrhythmic action is unknown, especially when chronic preventive treatment is considered where triggering events are probably important. Nevertheless, the profound electrophysiologic changes resulting from antiarrhythmic drugs alter several delicate balances, at the cellular level (repolarizing and depolarizing currents) and at the tissue level (refractory period/conduction time ratio). Some afterdepolarizations can be elicited, especially when repolarization is delayed by long cycle lengths and K+ current inhibition; reentry is enhanced when conduction impairment occurs without similar change in refractoriness. Proarrhythmic effects of drugs seem to relate to these alterations and caution should be exerted when ECG shows drug-induced QT or QRS prolongations.