Patients with atrial fibrillation (AF) face an annual stroke risk of about 5%. Evidence that anticoagulants reduce the risk of stroke has evolved over the 20th century. The American College of Chest Physicians (ACCP) has played a critical role in presenting guidelines for stroke prevention in AF. This commentary highlights the role that the ACCP guidelines have played, from their inception to the ninth edition. The first ACCP Conference on Antithrombotic and Thrombolytic Therapy in 1986 developed evidence-based guidelines for the indications, dosage, and monitoring of antithrombotic therapy. The conference recommended that anticoagulants be monitored by the international normalized ratio, and the appropriate dosage was to increase the international normalized ratio to two to three times control. This recommendation was widely accepted. Anticoagulants were recommended for AF with mitral valve disease and for nonvalvular AF with a history of embolism. No recommendations were made for nonvalvular AF without a history of embolism. These recommendations stimulated numerous randomized controlled trials (RCTs). By the third ACCP conference in 1992, RCTs had demonstrated a dramatic 69% stroke reduction in patients with nonvalvular AF. The third ACCP conference was the first to strongly recommend anticoagulation for primary and secondary stroke prevention in nonvalvular AF. ACCP conferences since 1992 have refined recommendations for nonvalvular AF on the basis of associated risk factors. The most recent conference, in 2011, recommended a direct thrombin inhibitor, dabigatran, rather than warfarin as the anticoagulant of choice. These ACCP guidelines have played a critical role in changing physicians’ practice patterns. In 1980 only 7% of patients with AF in the United States received OA; by 2007, this had increased to 57%.