Selective inhibitors of specific coagulation factors represent a new class of antithrombotic agents, designed to overcome the limitations of traditional anticoagulants. Available clinical studies indicate that the most promising new anticoagulants are those selectively targeting factor Xa and thrombin. Typically, the standard steps for clinical evaluation of new anticoagulants are thromboprophylaxis in high risk orthopedic surgery, followed by treatment of established venous thromboembolism, nonvalvular atrial fibrillation and acute coronary syndromes. These agents - that have the potential to be more effective and easier to use than conventional drugs such as heparins and vitamin K antagonists - will greatly expand our armamentarium for the prevention and treatment of arterial and venous thromboembolism. The current knowledge on these antithrombotic agents is summarized in this review, particularly focusing on the early results of clinical trials.