Electrophysiological characteristics of atrial cells (action potential duration and refractoriness, conduction speed) are modulated differently by vagal and sympathetic influences. The former tends to favour macro-reentry phenomena whereas the latter favours abnormal automaticity and triggered activity. In normal hearts vagal influences are predominant, thus explaining that the clinical pattern of vagal-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. Symathetically 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 suspecting which type of physiological autonomic predominance contributes to destabilize the arrhythmogenic substrate, but observing the behaviour of sinus rate variability just preceding the onset of the arrhythmia only permits documentation of the mechanism. The role of the 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, according to the causal mechanism, so that the choice of their use as a single or a combined therapy should be appropriate.