Apixaban is a highly selective, reversible, direct factor Xa inhibitor that inhibits both free factor Xa and prothrombinase activity, and clot-bound factor Xa activity. A predictable pharmacokinetic profile, multiple pathways of elimination, an improved bleeding profile relative to warfarin with a lack of other significant adverse events, and no need for routine anticoagulation monitoring make apixaban appealing. Apixaban is currently approved for venous thromboembolism (VTE) prophylaxis in total hip replacement and total knee replacement in Europe, Brazil, Australia, and New Zealand, and has been pre-approved in Indonesia and the Philippines. Completed phase 3 trials suggest that apixaban has promise as an alternative to aspirin and warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. Results of a large phase 3 trial were the first to show a survival benefit for this new class of oral anticoagulants in patients with atrial fibrillation. In patients with acute coronary syndrome, apixaban added to dual antiplatelet therapy with aspirin and clopidogrel resulted in unacceptably high rates of major bleeding. In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin, and was associated with significantly more major bleeding events than enoxaparin. Ongoing phase 3 trials will provide data regarding the efficacy and safety of apixaban for treatment of acute deep vein thrombosis and pulmonary embolism.