Vitamin K antagonists, such as warfarin, have been the anticoagulants of choice for many years for patients with AF and other thrombotic conditions. The introduction of direct oral anticoagulants (DOACs) as alternatives represents a major advance in anticoagulation. DOACs have been found to be at least as safe and effective as vitamin K antagonists in randomised, controlled trials for stroke prevention in AF and the management of venous thromboembolism, with real-world data showing similar outcomes. With the availability of several agents, selecting the most appropriate DOAC can be challenging. The aim of the present article is to provide useful guidance on the implementation of DOAC treatment in clinical practice.