Abstract The optimal management approach for patients with non–ST-segment elevation acute coronary syndromes continues to be an issue of debate. An ischemia-guided strategy appears to be effective as an alternative to either a very conservative “wait-and-see” approach or a very aggressive routine revascularization approach. The need for another approach is supported by the lack of conclusive evidence-based results favoring an early routine invasive treatment strategy. In the Thrombolysis in Myocardial Infarction (TIMI) IIIB trial, there were no differences in the incidence of death or myocardial infarction (MI) between patients treated with an early invasive approach and those treated with a conservative approach to treatment. Significantly worse outcomes were shown in patients assigned to an early invasive strategy in the Veterans Affairs Non–Q-Wave Infarction Strategies in Hospital (VANQWISH) trial at 1-year follow-up (111 clinical events in the invasive group vs 85 in the conservative group; p = 0.05). Registry information, including that from the Organization to Assess Strategies for Ischemic Syndromes (OASIS), which included approximately 8,000 patients with unstable angina or suspected MI, has even suggested an excess hazard with a routine invasive approach. Patients with non–ST-segment elevation MI observed in the Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO)-IIB and Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trials also fared better with an ischemia-guided strategy. Even the recent FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) trial investigators had to be very selective relative to eliminating high-risk patients in the first week and treating with intense anti-ischemic therapy and 5–7 days of low-molecular-weight heparin therapy to show an advantage for assigned revascularization. A careful clinical evaluation with attention to early risk stratification is essential in the ischemia-guided approach. The Braunwald classification for unstable angina helps identify independent clinical predictors of a poor outcome; high risk is clearly associated with Braunwald class III and type C. Electrocardiographic and biochemical markers for myocardial necrosis (cardiac troponin T or I) are important tools for assessing the presence and degree of ischemia and associated risk for adverse outcome. Noninvasive evaluation of left ventricular ejection fraction is essential for identifying those at high risk due to impaired contractile function. When these conventional markers do not provide conclusive information, noninvasive stress testing is most helpful to further identify those at highest risk for revascularization.