Atrial fibrillation (AF) is a major and widely recognized risk factor for cardioembolic stroke. Prophylactic therapy for the prevention of stroke in patients with AF is often achieved through oral anticoagulation, specifically with warfarin, which has been used for this purpose for more than 50 years. Although warfarin therapy is effective when implemented appropriately, it is often underutilized and requires consistent monitoring to ensure both safety in avoiding bleeding and efficacy in preventing strokes. Because the burden of AF-related stroke continues to rise, healthcare professionals need to understand the strengths and limitations of current and emerging treatment options. This review outlines current practices for managing the risk of stroke with anticoagulation in patients with AF, and discusses how new oral anticoagulants may affect clinical practice.