Atrial fibrillation (AF) is the most prevalent arrhythmia and its clinical incidence is on the rise. AF causes significant morbidity and mortality leading to rising AF-related health care costs. There is strong experimental and clinical evidence from animal and human studies that confirms the crucial role played by the renin angiotensin system (RA) in the etiopathogenesis of AF. Genetic polymorphisms of the ACE and aldosterone synthase genes have been linked to the development of AF in subjects with pre-existent risk factors for AF such as systemic hypertension and heart failure. This review appraises the current understanding of RAS antagonism, using angiotensin converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB) and aldosterone antagonists (AA), for prevention of AF. RAS antagonism has proven to be very effective for primary and secondary prevention of AF in subjects with heart failure and left ventricular (LV) dysfunction. The evidence for prevention in subjects without heart failure and with normal LV function is not as robust. RAS antagonism as an adjunct to antiarrhythmic medications is effective in reducing post-cardioversion AF recurrence. However, RAS antagonism in subjects undergoing catheter ablation has not been shown to be effective in preventing recurrences. ACE-I and ARB are equally effective in preventing AF and the addition of ARB to ACE-I therapy does not seem to confer an incremental benefit for AF prevention. The rising burden of AF and the strong evidence indicating a causative role for RAS in its etiopathogenesis necessitates ongoing research in this field to identify novel targets for intervention and develop effective therapeutic strategies.