The electrophysiologic characteristics of atrial cells (action potential duration and refractoriness, conduction speed) are modulated differently by vagal and sympathetic influences. The former tend to favor macroreentry phenomena, whereas the latter favor abnormal automaticity and triggered activity. In normal hearts, vagal influences are predominant, thus explaining why the clinical pattern of vagally mediated paroxysmal atrial fibrillation is preferentially observed in the absence of detectable heart disease, in young male adults, with an ECG pattern of common flutter alternating with fibrillation. Sympathetically mediated atrial fibrillation is observed in the presence of any heart disease, the first effect of which is to provoke a vagal withdrawal. The clinical history is a reliable guide for determining which type of physiologic autonomic predominance contributes to destabilization of the arrhythmogenic substrate, but observing the behavior of sinus rate variability just preceding the onset of the arrhythmia only permits documentation of the mechanism. The role of autonomic influences should be taken into consideration every time conventional antiarrhythmic treatment is insufficient. Beta blockers as well as digitalis may be either beneficial or detrimental, depending on the causal mechanism, so the choice of their use as a single or a combined therapy should be appropriate.