Morbidity and mortality associated with atrial fibrillation are mainly related to thromboembolic complications, particularly ischemic strokes. The prevention of thromboembolism is an important component of the management of patients with atrial fibrillation. The choice of optimum antithrombotic therapy for a given patient depends on the risk of thromboembolism, on the one hand, and the risk of intracerebral hemorrhage, on the other hand. Concerning the benefit-to-risk stratification, the problem lies in the similar and sometimes even identical risk factors for both thromboembolism and hemorrhage.At present, oral vitamin K antagonists are recommended for patients with atrial fibrillation at moderate or high risk of ischemic stroke. The thromboembolic risk should be assessed using validated stratification schemes, such as the CHADS(2) score for basic orientation and the CHA(2)DS(2)VASc score for extended risk stratification. Aspirin alone is recommended for patients at low risk of thromboembolic complications. Problems in antithrombotic therapy of atrial fibrillation arise treating those patients undergoing percutaneous coronary intervention and stent implantation, those with contraindication for vitamin K antagonists, or those with persisting left atrial thrombus requiring electrical cardioversion. The optimum therapeutic management of these special patients has not yet been defined by proper studies, leaving only empirically based recommendations for their treatment.Hopefully the development of new antithrombotic agents, that are easier to use and have a superior benefit-to-risk ratio, will extend effective prevention of thromboembolic events to a greater part of the atrial fibrillation population at risk.