Atrial fibrillation (AF) is the most commonly occurring arrhythmia. An antithrombotic agent is considered mandatory as part of the management in most patients with AF. It has been conclusively demonstrated that long-term anticoagulation therapy can significantly reduce the risk of stroke in patients with non-valvular AF. While vitamin K antagonists (VKAs) such as warfarin are highly effective, they possess numerous limitations that curtail their use, or make their use challenging for clinicians and patients. A new generation of anticoagulants are being investigated in clinical trials in patients with AF. One or more of these agents have the potential to either replace or act as alternatives to VKA therapy in AF. This review summarizes the recent accumulated evidence on anticoagulation to prevent the thromboembolism in patients with non-valvular AF. (Korean J Med 2011;81:434-443)