Although standard anticoagulation, including heparins and vitamin K antagonists (VKA), is clinically beneficial, several unmet needs remain due to several pharmacokinetic and pharmacodymamic limitations. Selective anticoagulant agents have been developed to overcome the drawbacks associated with both heparins and VKA. Agents selectively targeting factor Xa, IXa and thrombin are alternative anticoagulants in the most advanced phases of clinical development. Compared to traditional anticoagulants these drugs have the potential to be more effective, safer and easier to use and to provide a more predictable dose response, without need for routine monitoring and dose adjustment. This review will summarize the current status of selective anticoagulant drugs, which are already licensed or being evaluated in advanced phases clinical studies for antithrombotic treatment in non-valvular atrial fibrillation, percutaneous coronary intervention and acute coronary syndromes, focusing on design and results of studies in these specific clinical settings.