Atrial fibrillation (AF) is associated with high risk of systemic thromboembolism leading to significant morbidity and mortality. Warfarin, previously the mainstay for stroke prevention in AF, requires close monitoring because of multiple food and drug interactions. In recent years, food and drug administration has approved several direct oral anticoagulants (DOACs) for use in patients with nonvalvular AF. These agents have not been studied in patients with valvular AF who are at an even higher risk of systemic thromboembolism. DOACs do not require frequent blood testing or changes in dosage except when renal function deteriorates, however, the lack of established antidotes for many of these agents remains a challenge. Also, currently there is no head-to-head comparison between these agents to guide clinical choice. This article discusses the advantages and disadvantages of currently approved oral antithrombotics in nonvalvular AF, with a special emphasis on the DOACs and their individual characteristics.