Diabetes represents an independent risk factor for coronary artery disease (CAD), and the prognosis in terms of survival rates is worse for diabetic patients who have CAD with respect to those with CAD but no diabetes. An acute coronary event represents a cause of death in more than 30% of diabetics. Experimental studies suggested that the increased incidence of myocardial infarction in diabetics is due to an increased risk of developing atherosclerotic plaque with subsequent ulceration and intracoronary thrombus formation. Structural abnormalities of the coronary vessel wall were associated with an abnormal pattern of coronary flow and of coagulation abnormalities: all these abnormalities explain the epidemiological evidence of widespread and severe vascular atherosclerotic disease in diabetics. Due to the extreme complexity of ischemic vascular disease in patients with diabetes, an optimal therapeutic strategy is based on the correction of elevated blood glucose and lipid levels, of blood pressure, of platelet and coagulation abnormalities and of any other risk factor. Both percutaneous and surgical myocardial revascularization have been proved equally effective for CAD treatment in diabetes, even though a recent randomized trial has shown a significantly improved outcome after surgical revascularization. More recently the characterization of the advanced glycation end-product receptor opened new perspectives in the treatment of the complications of diabetes, and gave a new impact to the need of further investigations, through new randomized trials, of the best therapeutic options for diabetic patients.