Platelets have traditionally been understood within the context of hemostasis and hemorrhagic disorders. However, with increasing procedures being performed in smaller vessels and with an increasing incidence of atherosclerosis, the often critical role platelets play is more evident. Platelets are no longer viewed as “scaffolding” for the events of the coagulation cascade but rather as important catalysts in hemostasis, thrombosis, and fibrinolysis. Improved understanding of platelet physiology has led to developments of pharmacologic adjuncts resulting in improved patency rates and improved patient outcomes. This review addresses the physiology of platelet function and the impact of new pharmacologic agents in percutaneous intervention.