Platelets have attracted a growing interest among basic scientists and clinicians, as they have been shown to play an important role in many physiological and pathophysiological conditions. Beyond hemostasis, platelets participate in wound healing, inflammation, infectious diseases, maintenance of the endothelial barrier function, angiogenesis, and tumor metastasis. Over the last 50 years enormous progress has been made in our understanding of the role of platelets in hemostasis. Platelets circulate in blood in a resting state, but they are able to react immediately upon a vessel wall injury by adhering to the exposed collagen, followed by platelet-platelet interaction to form a plug that effectively seals the injured vessel wall to prevent excessive blood loss. Comparable events will take place on a rupturing atherosclerotic plaque, which may result in a platelet-rich thrombus. This chapter will address the molecular basis of platelet adhesion and aggregation, the regulation of platelet function and the interaction of primary and secondary hemostasis.