Non–vitamin K antagonist oral anticoagulants, also known as direct oral anticoagulants, are a relatively recent class of medications introduced into clinical practice. Due to their safety profiles, fixed dosing, and lack of need for frequent laboratory monitoring, they are becoming preferred to traditional anticoagulation with warfarin in many cases of nonvalvular atrial fibrillation and venous thromboembolism. Currently, four drugs are available: dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, factor Xa inhibitors. This review covers the pharmacology, monitoring, and reversal agents currently available for these medications. The indications for their use are covered through a review of the major clinical trials that led to their US and European approvals for clinical use. Perioperative management of these medications is discussed. Tables list indications, dosing, and monitoring, as well as bleeding risks and efficacy compared with warfarin. This review contains 1 figure, 11 tables, and 70 references. Key words: apixaban, dabigatran, direct oral anticoagulant, edoxaban, rivaroxaban