Acute coronary syndromes are a frequent cause of hospital admission for patients with coronary artery disease. The pathophysiology of acute coronary syndromes often involves plaque rupture or fissure with platelet aggregation. Recognition of the importance of platelet aggregation resulted in several large randomized trials testing 3 types of platelet antagonists, aspirin, glycoprotein IIb/IIIa inhibitors, and adenosine diphosphate inhibitors. A thorough understanding of the data, risks, and benefits of these therapies is important to optimize treatment of the patient with an acute coronary syndrome. Recognition that there is a great deal of interpatient variability in response to these antiplatelet therapies highlights the need for future research in this area.