Epidemiologic studies have shown that atrial fibrillation (AF) raises the risk of stroke approximately fivefold, and that because AF is so common among the stroke-prone elderly, it accounts for about 15% of all strokes. Five recently completed, randomized trials consistently found that the anticoagulant warfarin can prevent most of the additional stroke risk due to AF. This effect was seen at low doses. The trials have also demonstrated that warfarin therapy can be safe if careful patient selection and monitoring are implemented. Three of the trials provided inconsistent, and currently inconclusive evidence about the efficacy of aspirin. The trials have not settled the anticoagulation decision for all patients. Warfarin remains a demanding and risky therapy, which many patients and physicians do not find attractive. Future research should attempt to refine the risk of stroke, and of major hemorrhage during warfarin therapy among patients with AF, and should seek safer, less demanding, yet effective antithrombotic regimens.