Decision-making about anticoagulation is among the most challenging aspects of atrial fibrillation (AF) management from the perspectives of both patients and physicians. On one hand, AF-related stroke, the most feared sequela of the arrhythmia, is more likely to be fatal or severely debilitating than strokes from other causes and can often be prevented with oral anticoagulants. On the other hand, anticoagulation causes major and minor bleeding, impacts quality of life, is costly to patients and the health care system, and has poor long-term compliance rates. Guidelines recommend lifelong anticoagulation on the basis of upstream risk factors irrespective of whether the AF burden is low from spontaneous termination or as the result of rhythm control strategies including antiarrhythmic drugs and ablation. This practice represents 1 example in medicine where identical treatment is administered without regard to the burden of disease or even in the face of disease diminution or resolution. Frequently cited reasons for this recommendation include the modest long-term success rates of rhythm control interventions, the high proportion of asymptomatic AF, and the uncertain role of the atrial myopathy that hypothetically may cause cardioembolic events independent of the arrhythmia. The rising prevalence of AF and the risks associated with this “1-size fits all” strategy make clear, however, that innovative approaches are needed and will haveincreasing importance over time.