Key pathophysiologic mechanisms of diabetes-related coronary disease include inflammation and a prothrombotic state. In the setting of non-ST-segment elevation acute coronary syndromes diabetic patients are at high risk for subsequent cardiovascular events. At the same time, they derive greater benefit than non-diabetic counterparts from aggressive antithrombotic therapy, early coronary angiography, and stent-based percutaneous coronary intervention. The mainstays of antithrombotic therapy for diabetic patients undergoing percutaneous revascularization include aspirin, clopidogrel, platelet glycoprotein IIb/IIIa receptor antagonists, and heparin or low-molecular-weight heparin. Despite dramatic reduction in restenosis conferred by drug-eluting stents, diabetic patients remain at increased risk for repeat revascularization. More efforts are needed both in terms of local drug elution as well as systemic pharmacologic therapies to further contain the excessive neointimal proliferation that characterizes the diabetic response to vascular injury.