The stroke rate in atrial fibrillation is 4.5% per year, with death or permanent disability in over half. The risk of stroke varies from under 1% to over 20% per year, related to the risk factors of congestive heart failure, hypertension, age, diabetes, and prior stroke or transient ischemic attack (TIA). Major bleeding with vitamin K antagonists varies from about 1% to over 12% per year and is related to a number of risk factors. The CHADS(2) index and the HAS-BLED score are useful schemata for the prediction of stroke and bleeding risks. Vitamin K antagonists reduce the risk of stroke by 64%, aspirin reduces it by 19%, and vitamin K antagonists reduce the risk of stroke by 39% when directly compared with aspirin. Dabigatran is superior to warfarin for stroke prevention and causes no increase in major bleeding. We recommend that all patients with atrial fibrillation or atrial flutter, whether paroxysmal, persistent, or permanent, should be stratified for the risk of stroke and for the risk of bleeding and that most should receive antithrombotic therapy. We make detailed recommendations as to the preferred agents in various types of patients and for the management of antithrombotic therapies in the common clinical settings of cardioversion, concomitant coronary artery disease, surgical or diagnostic procedures with a risk of major bleeding, and the occurrence of stroke or major bleeding. Alternatives to antithrombotic therapies are briefly discussed.