Cardiovascular diseases are one of the major causes of mortality in the western world. As platelet dependent thrombosis is of central importance in their pathophysiology, several successful strategies, targeting a specific platelet function or interaction, have been developed to prevent or treat these disorders. However, as the current antiplatelet strategies are limited in efficacy and safety, and often influence normal haemostatic functions, new compounds are being developed with improved characteristics. This review deals with the development of novel antiplatelet compounds for which evidence is available on their antithrombotic action in vivo. In a first part, these compounds, their targets and their potential applicability are discussed. The second part of this review focuses on BT tests and bleeding models and their usefulness for determination and / or prediction of the safety of novel antiplatelet compounds.