Hemostasis is a normal process preventing the sequelae of uncontrolled hemorrhage. In certain settings, these same processes cause adverse clinical events due to thrombotic occlusion of a vessel. The majority of unstable coronary syndromes result from disruption of an atherosclerotic plaque, leading to the exposure of subintimal contents, which triggers coagulation and the formation of a platelet-rich thrombus. The central role of platelet activation in the events that lead to vessel occlusion is well known. However, this process is complex and influenced by a myriad of cellular and plasma-derived mediators that regulate the balance between occlusive and nonocclusive thrombosis.