- Atrial fibrillation (AF) is the most common sustained arrhythmia in Western countries (prevalence 1-2%). Patients with AF have a 5-fold increased risk of stroke, and 15%-20% of all strokes are attributable to AF. Moreover, mortality, morbidity and economic burden from stroke complicating AF are particularly high. Thus, preventing stroke and thromboembolism is the cornerstone in AF management, with the vitamin K antagonist (VKA) - warfarin as the leading drug for many years. Although warfarin is effective in stroke reduction, only 55% of eligible patients with AF received it, 28% of patients discontinue it by 1-year, rates of major bleeding are higher that 20% and patients remain in the therapeutic range (INR 2-3) only 58% of the time. Warfarin underuse results from its pharmacological properties including: genetic variability in metabolism, multiple drug and food interactions, unpredictable anticoagulant effects, narrow therapeutic window, and the resulting need for inconvenient monitoring. The combination of aspirin and clopidogrel was found to be less effective than warfarin. Hence, new treatments were recently evaluated for AF-related stroke and thromboembolic prevention including: direct thrombin inhibitors (dabigatran etexilate), oral selective factor Xa inhibitors (rivaroxaban and apixaban), and percutaneous left atrial appendage closure. Some of these drugs have demonstrated promising results in clinical studies, they are convenient to use and do not require monitoring. The downsides are lack of antidotes or specific blood assays to monitor the anticoagulant effect and the need for invasive procedure for installation. Herein, we review the new treatments and the available clinical evidence for their use in AF.