The benefits of aspirin use in the emergent care of MI and stroke have been well established. Recent studies have further demonstrated the importance of antiplatelet therapy in the acute setting, primarily with the use of intravenous glycoprotein IIb/IIIa receptor inhibitors. Aspirin and the thienopyridines (ticlopidine and clopidogrel) are oral antiplatelet agents that interfere with platelet activation in complementary, but separate pathways. Combination therapy of clopidogrel and aspirin has demonstrated benefit for the management of acute coronary syndromes, ischemic cerebrovascular disease and peripheral vascular disease in several large trials [1,2]. This article reviews the pathophysiology of platelet activation, landmark trials on oral antiplatelet agents, and the current recommendation for the use of oral antiplatelet agents in the emergency department