Acute coronary syndromes reflect a spectrum of disease related, most commonly, to the sudden reduction in blood flow to a portion of myocardium. The underlying pathogenesis of the reduction in coronary flow is related to the sudden rupture of an atherosclerotic plaque, with subsequent thrombus formation leading to either vascular occlusion or microembolization. Clinicians combat this process with antithrombotic therapy, which typically includes both anticoagulant and antiplatelet therapy, and mechanical therapies, such as percutaneous coronary interventions, nearly always using stents. This review focuses on P2Y12 antagonists as one component of our armamentarium of antiplatelet therapies, specifically on data addressing in whom, when, which agent, and in what dose such agents should be administered.