The American College of Cardiology and American Heart Association have updated their guidelines for the management of non–ST-segment-elevation acute coronary syndrome for the first time since 2002. In the interim, several important studies affecting choices of therapy potentially begun in the emergency department have been completed, and care patterns have changed and matured significantly. In this review, we present the new recommendations that are pertinent to emergency medicine practice and comment on their potential implementation into an evidence-based, multidisciplinary approach to the evaluation and management of this challenging patient population. [Ann Emerg Med. 2008;51: 591-606.]