Platelets are involved in haemostasis and vessel integrity under physiologic conditions, and in thrombosis under disease states. Platelet activation upon stimulation with various agonists in vitro and in vivo, is strongly dependent on an increase of intracellular Ca(2+) concentration. The latter results from Ca(2+) release by the dense tubular system (DTS), and Ca(2+) entry from the extracellular space. Recent advances in identification of the molecular mechanisms involved in these processes are described in this review, along with potential targets for pharmacologic interventions in disease states.