P LATELETS CIRCULATE passively as they traverse the vascular tree that is lined by an intact monolayer of endothelial cells. In response to vessel wall injury or exposure to foreign surfaces, platelets rapidly undergo the processes of adhesion, shape change, secretion, and aggregation through a series of exquisitely coordinated responses that culminates in the formation of a precisely localized hemostatic plug. The state of platelet activation is dynamically modulated by the balance of actions of a diverse array of excitatory and inhibitory signals to which the platelet surface may be exposed. Platelets are equipped with specific plasma mem-brane receptors that can recognize and organize these vanous stimuli. Initiated by receptor occupancy, the positive and negative extracellular signals are rapidly translated into complex biologic responses through processes of signalresponse coupling mediated by a remarkably limited nepertome of intracellular second messengers(Fig 1). This review summarizes our current understanding of the biochemical pathways of platelet activation and inhibition, with specific emphasis on recent advances and unresolved issues. Several previous reviews have provided descriptions of various aspects of extnacellular signal transduction.’4