Arterial thrombosis, manifesting as acute myocardial infarction or ischaemic stroke, is the single most common cause of morbidity and mortality in industrialised societies. Platelets are a pre-requisite for the formation of arterial thrombi and, as a consequence, novel antiplatelet agents are sought to meet the significant clinical need for a potent, safe, and orally available therapy for the management of cardiovascular disease. Platelet thrombin receptors, termed protease-activated receptors (PARs), represent one promising candidate for the development of such therapy. This review outlines the role of platelet PARs in haemostasis and thrombosis and discusses the preclinical and clinical evidence supporting the potential of PAR antagonists as novel antiplatelet therapy.