Atrial fibrillation comprises a large and growing epidemic in the aging population. Stroke is the most feared complication of atrial fibrillation, and the risk of stroke increases markedly with age. Multiple clinical trials have proven that warfarin anticoagulation is effective in reducing this risk. However, the complex pharmacokinetics and narrow therapeutic window of warfarin make its use in clinical practice challenging. Novel approaches to anticoagulation, including more potent antiplatelet agents and direct thrombin inhibitors, are currently undergoing clinical trials. In addition, nonpharmacological approaches to stroke prevention in atrial fibrillation are also in development. These newer approaches may revolutionize the treatment of this common disorder.