In 2014, the American Heart Association and the American College of Cardiology (AHA/ACC) published their guideline for the management of patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS), whereas the European Society of Cardiology published their latest guideline for the management of patients with NSTE-ACS in 2011. In this article, we review the main updates in antiplatelet and anticoagulation therapy in the 2014 AHA/ACC guideline and compare them with the 2011 European guidelines. Key recommendations in the AHA/ACC guidelines include the addition of ticagrelor to a broad spectrum of patients with NSTE-ACS, narrowing of the role of prasugrel to patients who undergo coronary stenting, and limiting the use of glycoprotein IIb/IIIa receptor inhibitors mainly to high-risk patients during percutaneous coronary intervention. These modifications bring the North American and the European guidelines closer together. The recommendations regarding anticoagulants still differ between the 2 guidelines, although all 4 parenteral agents (unfractionated heparin, low-molecular-weight heparin, bivalirudin, and fondaparinux) are now considered acceptable by both guidelines. We also review new data from clinical trials that became available after the 2014 guidelines were finalized, including studies with cangrelor, rivaroxaban, vorapaxar, ticagrelor, and long-term use of dual antiplatelets that will be considered in future guidelines. As the 2014 guidelines represent the most comprehensive and authoritative document for the management of patients with NSTE-ACS, clinicians who manage these patients should be familiar with their recommendations to ensure optimal patient care.