Atrial fibrillation continues to be a challenging arrhythmia. There are some conventional, time-tested explanations of atrial fibrillation genesis, however some uncertainty of its complete understanding still exists. We focused on atrial ischemia which, hypothetically, could be responsible for manifestation of the arrhythmia, irrespective of the underlying heart disease. Evidences abounds that atrial fibrillation has an extremely strong association with nutritional/oxidative status of myocardium. This arrhythmia seemingly may stem from the electrophysiological differences taking place in the boundary areas. To validate such assumptions we have surveyed widely accepted theories based on clinical and experimental evidence. There was an attempt to integrate some well-known theoretical explanations (focal, multifocal, ectopic, reentrant activity, atrial remodeling, etc.) into a new conceptually systematized arrhythmogenesis. Confronting ischemic and non-ischemic atrial zones electrophysiologically on their borderlines presumably creates a substrate vulnerable to the development of atrial fibrillation. The behavior of these interrelated areas is likely ischemia-dependent; the separating borderline(s) may be treated as conflictogenic, releasing triggers/drivers to commence and to perpetuate the arrhythmia. Ischemically damaged and non-damaged myocardial areas likely participate in the relay-race carousel of arrhythmogenicity due to their mutual interactions, accompanied by the “fireworks” at the separating borderlines. It could be concluded that myocardial ischemia as a nonspecific proarrhythmic factor presumably plays a key role in the genesis and sustenance of atrial fibrillation. Theoretically the most important step in eradication of arrhythmogenic substrate might be an overall abolition of ischemia regardless of the characteristics of underlying heart disease. Innovative intellectual and explorative research is needed to render innocuous the ischemia that might help us win the century’s cardioarrhythmological battle.

Abbreviations: AF= atrial fibrillation, PV= pulmonary vein, IDCAF= ischemia-dependent conflictogenic atrial fibrillation