Cardiovascular disease remains a leading cause of morbidity and mortality among Americans. A significant share of all resources for health care is allocated for the diagnosis and treatment of acute coronary syndrome (ACS), including ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina. Because millions of patients visit emergency departments with chest pain and other symptoms that might indicate ACS, the clinician must be familiar with appropriate diagnostic and therapeutic treatment measures. Non-ST-segment elevation (NSTE) ACS is a particularly challenging clinical entity due in part to limitations in the diagnostic tools employed to detect it and the wide range of therapeutic options available to treat it. Despite advances in the treatment of ACS and the dissemination of formal recommendations on approaches to managing NSTE ACS, pharmacologic and reperfusion therapy remain underused and often delayed. This results in an increase in adverse cardiac events for patients and rising health care costs for the public. The key to NSTE ACS management is rigorous adherence and application of evidence-based recommendations. The American Heart Association (AHA) and the American College of Cardiology (ACC) have released comprehensive clinical practice guidelines to manage NSTE ACS. These include a process of risk stratification of patients presenting with NSTE ACS or possible NSTE ACS. Risk stratification can be performed using a number of scoring models, including the Thrombolysis in Myocardial Infarction (TIMI), the Global Registry of Acute Coronary Events (GRACE), and the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) scoring models. Once a patient's risk for adverse cardiac events is determined, appropriate diagnostic and therapeutic modalities can be selected to match their level of risk. American College of Cardiology/AHA recommendations for the diagnosis and treatment of NSTE ACS include considerations regarding admission, antiplatelet therapy, anticoagulation, and early percutaneous coronary intervention/diagnostic angiography with the intent to perform revascularization. New information has emerged since the release of the 2007 updated ACC/AHA guidelines. The 2009 update of the ACC/AHA guidelines includes new recommendations on antiplatelet therapy, early invasive therapy, and the timing of glycoprotein IIb/IIIa inhibitor therapy for patients with NSTE ACS. Considering this new information during the application of the ACC/AHA guidelines will enhance selecting the optimal treatment for the NSTE ACS patient and ensure appropriate use of health care resources.