Current treatment guidelines recommend an early, aggressive strategy in patients with non–ST-elevation acute coronary syndromes. Administration of antiplatelet therapy—a glycoprotein IIb-IIIa inhibitor with or without clopidogrel—before catheterization in patients with high-risk features confers substantially reduced risk of ischemic events while potentially increasing bleeding risk. Strategies for risk stratification are therefore important in the emergency department, with appropriate pharmacotherapy. This review will examine implications of the new guidelines for management of patients with unstable angina/non–ST-elevation myocardial infarction for emergency physicians, review current risk stratification paradigms, and evaluate appropriate use and timing of administration of glycoprotein IIb-IIIa inhibitors and clopidogrel for patients at varying levels of risk. We will also examine mechanisms for generating institutional care pathways that can enhance consistency and quality of care as well as communication among members of the medical team responsible for caring the patient with acute coronary syndrome.