Platelet glycoprotein (Gp) IIb/IIIa receptor antagonists improve outcomes in patients with acute coronary syndromes without persistent ST-segment elevation, but relative effects depend on appropriate patient selection. Recent data from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines) quality improvement initiative suggests that GpIIb/IIIa antagonists are underused in clinical practice. The relationship between GpIIb/IIIa inhibition and the magnitude of clinical benefit in the setting of acute coronary syndromes is complex. Several key factors should be considered for proper patient selection, including accurate patient risk stratification, incorporation of these agents with an early invasive management strategy and the concomitant use of other anti-thrombotic therapies. Current practice guidelines for the treatment of patients with non-ST-segment elevation acute coronary syndromes support the integration of an early invasive management with optimal pharmacological therapy, including GpIIb/IIIa antagonists.