The American College of Cardiology, American Heart Association, and the European Society of Cardiology published updated guidelines in 2007 for patients with non-ST elevation acute coronary syndrome. In this article, we review the recommendations for antiplatelet therapy and supporting data, highlight new changes, and describe differences between the European and North American guidelines. The new guidelines provide more details regarding the selection of an early conservative versus an early invasive approach based on the patient's profile and balance between ischemic and bleeding risks. Important new recommendations include wider endorsement for low-dose aspirin maintenance therapy, longer duration of clopidogrel following percutaneous coronary intervention, additional guidance regarding surgery in selected patients on clopidogrel, identification of patients most likely to benefit from glycoprotein IIb/IIIa inhibitors (with appropriate dose modification in patients with renal failure), and the option to use early clopidogrel with bivalirudin in patients managed invasively who are at increased risk of bleeding. The new guidelines also discourage the concomitant use of nonsteroidal anti-inflammatory drugs and delineate indications for adding warfarin to antiplatelet therapy. Because antiplatelet therapy is the cornerstone of management of patients with non-ST elevation acute coronary syndrome, health care providers should make themselves familiar with the new data and latest guideline recommendations.