Novel oral anticoagulants, including dabigatran, rivaroxaban, and apixaban, represent new options for preventing stroke in patients with atrial fibrillation, as shown by the results from large, randomized phase III trials. Because of their greater specificity, rapid onset of action, and predictable pharmacokinetics, the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) address several limitations of warfarin or other vitamin K antagonists in day-to-day clinical practice. However, a range of practical questions relating to the novel oral anticoagulants has emerged, including topics such as patient selection, treatment of patients with renal impairment, risk of myocardial infarction, drug interactions, switching between anticoagulants, and management of bleeding, in addition to use of these agents in patients requiring antiplatelet drug treatment or undergoing cardioversion or percutaneous interventions (eg, ablation). In this review, practical aspects of the use of novel oral anticoagulants in patients with atrial fibrillation are discussed, with reference to available data and guidance from prescribing information.