Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with potentially dreadful cardioembolic complications such as stroke. The risk of stroke is stratified based on the patient’s comorbid conditions using several scoring systems. Patients are treated with oral anticoagulation using warfarin or aspirin based on their cardioembolic stroke risk. Although warfarin has been the only effective therapy, it is underutilized clinically due to concern for multiple drug-to-drug a d drug-to-food interactions and hemorrhagic complications. Dual antiplatelet therapy with aspirin and clopidogrel has been studied as a potential alternative anticoagulant for AF patients; however, the combination of aspirin and clopidogrel was noted to be inferior to warfarin in preventing strokes, with an increased risk of bleeding. As a result, newer anticoagulant agents, including direct thrombin inhibitors, direct and indirect factor Xa inhibitors, and vitamin K antagonists, have been developed and evaluated in AF patients. Results from a recent study demonstrated that high-dose dabigatran, a direct thrombin inhibitor, was superior to warfarin in preventing stroke and systemic embolism with similar bleeding risk. It ultimately received approval by the US Food and Drug Administration for stroke prophylaxis for nonvalvular AF patients. There are several other direct factor Xa inhibitors currently under study. Dabigatran may be considered in AF patients who are intolerant to warfarin or unwilling or unable to follow-up with frequent laboratory monitoring. Other newer anticoagulant agents also provide us with possible suitable alternatives to warfarin, and their clinical use will depend on the results from ongoing studies.