Anticoagulant drugs are traditionally administered for the prevention and treatment of thrombosis. Besides multi-targeted, traditional anticoagulants, such as coumarins or heparins, the search for the optimal antithrombotic efficacy to bleeding risk ratio has prompted the development of a novel armamentarium of anticoagulant drugs, which is expected to be introduced in the market. These emerging drugs are mainly targeted to suppress the propagation of the coagulation cascade (thrombin burst), by direct thrombin inhibition or selective inhibition of activated factor X. Therefore, thrombin or activated factor X antagonists would produce an efficient anticoagulation while minimizing the risk of bleeding, the most common adverse events of conventional anticoagulants. No routine monitoring, favorable form of administration and better compliance are additional advantages of these innovative drugs, which are already in advanced development or already licensed for clinical use. The aim of this article is to provide an overview on the mechanisms of action, clinical applications, cost-effectiveness and side effects of these emerging anticoagulant strategies.