Atrial fibrillation (AF) is a risk factor for ischemic stroke. In randomized trials, AF raised the risk of stroke nearly sixfold, cumulating in a 35% risk over a lifetime. Anticoagulation with warfarin reduces the danger of ischemic stroke, but carries hemorrhagic risks, making this agent unsuitable for treating many patients. Platelet inhibitor therapy with aspirin was highly effective for patients younger than 75 years of age in one study, but the reason for lower efficacy in older individuals is perplexing. These trials support a thrombotic mechanism for most strokes in patients with AF, but leave physicians in a quandary as to selection of optimum prophylaxis. Secondary analysis of patients given placebo identified predictors of thromboembolism, including a history of hypertension, congestive heart failure, and prior stroke or transient ischemic attack, and echocardiographic findings of left ventricular dysfunction or left atrial enlargement. The absence of these risk factors selects a fairly large subgroup of AF patients at comparatively low risk of stroke, for whom the danger and inconvenience of chronic anticoagulation may not be warranted. It is becoming clear that specific clinical and echocardiographic features allow individualized antithrombotic approaches within the broad category of patients with AF, to enhance therapeutic benefit while minimizing hemorrhagic risk.