Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. AF is a potent risk factor for stroke and systemic thromboembolism. Patients with AF have been observed to have a worse outcome following stroke, therefore prevention of stroke in patients with AF is of paramount importance. Antithrombotic therapy is crucial for prevention of stroke in patients with AF. Vitamin K antagonists (VKAs) have been the traditional anticoagulants for prevention of stroke in patients with AF. Drug treatment with VKAs is associated with significant management issues, such as an unpredictable dose response necessitating dose adjustments, frequent laboratory monitoring and multiple interactions with other drugs. Despite following best practices, VKAs are associated with limited efficacy and increased risk of hemorrhage.  Due to these limitations a significant effort has been devoted towards development of newer anticoagulants. Dabigatran, Rivaroxaban, and more recently Apixaban have been approved by the F.D.A. for the prevention of stroke in patients with AF. These newer agents possess highly predictable pharmacokinetic and pharmacodynamics properties which allow a fixed dosing regimen and also eliminate the need of routine laboratory monitoring. This review discusses various anticoagulants for prevention of stroke in patients with AF.