Four non-vitamin-K antagonist oral anticoagulants (NOACs) are now available and are variously approved for stroke prevention in atrial fibrillation and the management of venous thromboembolism. On the whole, these drugs offer clear benefits over warfarin, overcoming problems with unpredictable individual responses and avoiding the need for frequent and resource-intensive monitoring. Sufficient data are now available to recommend the use of particular NOACs in defined settings. As a group these drugs offer a real alternative to warfarin; their more widespread use for stroke prevention in atrial fibrillation, in the management of venous thromboembolism, and perhaps in other settings promises to bring real clinical gains for at-risk populations worldwide. This review highlights the growing importance of effective anticoagulation therapy at a time when cardiovascular risk profiles are evolving, discusses the relative merits of the NOACs over warfarin, and describes the use of specific agents in specific patient populations.