Cerebrovascular accidents related to atrial fibrillation (AF) are potentially preventable with anticoagulation. Until recently, warfarin was the only proven anticoagulant to be effective in stroke prevention, however the novel, direct acting oral anticoagulants (DOACs) are now available, triggering a paradigm shift in treatment philosophy. Today, physicians need to consider in which patients anticoagulation should not be used rather than, as in the past, deciding in which patients it should be used. Although warfarin will continue to have a place in managing some patients with AF, in the future, the DOACs should be the predominant therapy for stroke prevention in patients with non-valvular AF.