Among patients presenting with suspected non-ST elevation acute coronary syndromes, sudden ECG changes, elevated levels of cardiac enzymes, and/or a Thrombolysis in Myocardial Infarction (TIMI) risk score of 3 or greater identifies those patients at risk for an unfavorable outcome. Institution of glycoprotein (GP) IIb/IIIa receptor inhibitor therapy as well as early invasive evaluation should be considered strongly in these patients. Based on clinical trials, pharmacokinetics, and logistical considerations, abciximab appears to be the superior agent in those patients undergoing truly early invasive therapy (fewer than 4 hours from presentation). When more prolonged medical therapy is feasible, preferred, and/or necessary before invasive evaluation, eptifibatide and tirofiban are our preferred agents in high-risk patients. Among patients at low risk or when the correct diagnosis is uncertain, we defer the addition of GP IIb/IIIa receptor inhibitor therapy pending prompt noninvasive or invasive evaluations to clarify the diagnosis.