Atherosclerotic heart disease is the leading cause of death in patients with diabetes mellitus. Platelets play a major role in the clinical manifestations of ischemic heart disease. Diabetic patients have hyperreactive platelets with exaggerated adhesion, aggregation and thrombin generation. Antiplatelet agents, including aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors, have shown significant efficacy in reducing recurrent ischemic events in patients with diabetes. Treatment with glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention reduces mortality in diabetic patients.