Atrial fibrillation (AF) is a growing public health problem associated with significant morbidity and mortality. Numerous randomized controlled trials of warfarin have conclusively demonstrated that long-term anticoagulation therapy can reduce the risk for stroke by approximately 68% per year in patients with nonvalvular AF, and even more in patients with valvular AF. However, available data show that of those patients with AF and no contraindication to warfarin therapy, only 15% to 44% are prescribed warfarin. Our literature review has identified patient-, physician-, and health care system-related barriers to warfarin prescription. However, the relative importance of these specific barriers remains unknown. Further work is needed to understand the discrepancy between the randomized controlled trial evidence and clinical practice patterns.