Thrombosis, both venous and arterial, is a major cause of morbidity and mortality worldwide. Consequently, there is an ongoing search for new antithrombotic drugs, particularly novel antiplatelet agents and anticoagulants. A better understanding of the biochemical pathways involved in platelet activation and coagulation and of the links between these systems and the impact of thrombosis on inflammation has led to the identification of new targets for antithrombotic drugs. This paper focuses on these new targets and new antiplatelet drugs and anticoagulants and describes the major advances in the continuing search for more potent antithrombotic drugs that have limited effects on hemostasis.