The role of platelet aggregation is pivotal in the pathophysiology of non-ST-elevation acute coronary syndromes. The inhibition of the platelet glycoprotein IIb/IIIa receptor has been shown to reduce adverse cardiac events in patients with non-ST-segment elevation coronary syndromes as well as patients undergoing percutaneous coronary interventions. Current data strongly favor the early "upstream" use of glycoprotein IIb/IIIa inhibitors in patients presenting with non-ST-elevation acute coronary syndromes, followed by an invasive strategy with diagnostic cardiac catheterization within 48 hours of admission. The benefit of early platelet inhibition is seen in patients who are managed medically and in those who undergo percutaneous or surgical revascularization. The benefit of the "upstream" use of glycoprotein IIb/IIIa inhibitors is not limited to hospitals with invasive capabilities, but extends to patients admitted to peripheral community hospitals. High-risk patients with positive serum markers of myocardial necrosis derive a particular benefit from an early aggressive platelet inhibition strategy followed by early angiography and revascularization. © 2003 CVRR, Inc.