Atrial fibrillation (AF) is a common arrhythmia in clinical practice. An important component of the management of patients with AF involves prevention of thromboembolism and stroke. Coumarins, such as warfarin had been the only available oral antithrombotic agent for prevention of thromboembolism for many decades. Following intestinal absorption, coumarins inhibit multiple steps of the clotting cascade that leads to inhibition of coagulation factors II, VII, IX and X. In addition to delayed and variable inhibition of coagulation, coumarin therapy has a narrow therapeutic window for optimal balance of risk and benefit, which requires regular assessment of the international normalized ratio (INR) to monitor coagulation. A quest for safer, more effective therapies that do not need monitoring has led to the development of dabigatran, rivaroxaban, and apixaban. In this article, we review these newer antithrombotic agents and discuss role of these drugs in clinical practice.