The only major and potentially fatal risk for patients with atrial fibrillation is the development of systemic thromboembolism. Stroke occurs five times more frequently in patients with atrial fibrillation than in comparable patients in sinus rhythm. The yearly incidence of stroke in atrial fibrillation largely depends on the underlying heart disease: from 0.5% in "lone" atrial fibrillation up to 20% in rheumatic heart valve disease. Oral anticoagulation with vitamin K antagonists dramatically reduces the stroke risk by two-thirds, but is a laborious and patient-unfriendly therapy. Oral direct thrombin blockers and oral factor Xa antagonists, both without therapy monitoring, may replace warfarin for this indication, but there are safety and efficacy issues to be resolved. Oral antiplatelet agents are effective, but clearly less than warfarin. Angiotensin receptor blockers are currently under investigation. Routine electrocardioversion for atrial fibrillation does not reduce the stroke risk, but promising techniques include electroablation of the left atrium and occlusion of the left atrial appendage.