Non-ST-segment elevation myocardial infarction (NSTEMI) is a major cause of cardiovascular morbidity and mortality in the United States. It represents the highest risk category of non-ST-segment elevation acute coronary syndromes (NSTEACS), for which timely diagnosis and appropriate therapy are paramount to improve outcomes. Evidence-based treatment, with combination of antiplatelet and anticoagulant therapy, and with serious consideration of early coronary angiography and revascularization along with anti-ischemic medical therapy, is the mainstay of management for NSTEMI. Aggressive risk-factor control after the acute event is imperative for secondary prevention of cardiovascular events. Applying in practice the American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations results in improved outcomes.