Atrial fibrillation (AF) arises as a results of a complex interaction of triggers, perpetuators and substrate. The recurrence of AF may be partially related to a biologic phenomenon known as remodeling, in which the electrical, mechanical, and structural properties of the atrial tissue and cardiac cells are progressively altered, creating a more favourable substrate. Atrial remodeling is in part a consequence of arrhythmia itself. Thereafter, to prevent and to treat AF, attention has been directed to upstream therapy, in order to alter the arrhythmia substrate and to reduce atrial remodeling; the most promising drugs seem to be those targeting the renin-angiotensin-aldosterone system (RAAS). As clinical evidence has developed, it has become clear that upstream therapies may have a different effect on primary and secondary AF prevention. Several post-hoc analyses from large trials, suggested the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II-receptor blockers (ARBs) in primary prevention of AF. Four meta-analyses have shown that risk of new-onset AF, particularly in patients with heart failure, was reduced, On the contrary, prospective, placebo controlled, randomised studies with ARBs returned negative results for secondary prevention of AF. The studies with ACEIs were few and individually very small. On the whole, in secondary prevention of AF, the studies accounting for about 90% of the ACEIs and ARBs population together have presented neutral results, without reduction of AF recurrences. The hypothesis of using RAAS inhibitors as antiarrhythmic drugs to prevent AF recurrences is declining since more and more negative trial results are published.