Atrial fibrillation (AF) greatly increases the risk of stroke. Long-term oral therapy with warfarin reduces the risk of AF-related stroke by 62%, and national guidelines now call for warfarin therapy in most patients without specific contraindications to anticoagulation. However, the drug's narrow therapeutic index means that warfarin therapy must be guided by coagulation monitoring. This requirement and other inherent limitations of warfarin have led to widespread underutilization and underanticoagulation in AF patients who require antithrombotic therapy for stroke prevention. Recent studies indicate that in many health systems less than half of warfarin-eligible patients take the drug and even fewer are adequately maintained within a protective therapeutic range. Similarly, despite the documented efficacy of anticoagulation in patients at risk for deep vein thrombosis (DVT) and related pulmonary embolism, prophylaxis for DVT, even in high-risk situations such as following orthopedic surgery, is suboptimal. This article explores the scope of warfarin underutilization and underanticoagulation that exists in current clinical practice. The clinical consequences of warfarin underuse are also described. Discussion in the roundtable after this review explores the causes for the wide treatment gap between anticoagulation clinical trial results and clinical practice outcomes. The economic implications of such a gap and strategies for closing the gap are also discussed by the panelists.