The prevalence of atrial fibrillation (AF) increases with age and is projected to escalate in coming decades as people have longer life expectancies. The burden of this disease has a substantial impact on healthcare costs and quality of life, particularly among AF patients who experience strokes. Until recently, the mainstays of stroke prophylaxis in patients with AF have been anticoagulation with warfarin or antiplatelet therapy with aspirin, depending on patient preferences, clinical risk stratification, and contraindications. However, the limitations of these conventional options, especially among elderly patients, have given rise to the first new oral anticoagulants in over half a century. Successful clinical trials have led to regulatory approval of several alternatives for clinical use. This article reviews the evidence supporting antithrombotic prophylaxis, describes current practice guidelines, and discusses the use of novel therapeutic options for elderly patients with nonvalvular AF.