Diabetes mellitus is a worldwide epidemic whose incidence and prevalence have significantly increased in recent decades. Diabetic patients have an increased mortality and morbidity related to ischemic heart disease and are more likely to develop multivessel coronary artery disease than non-diabetic patients. An acute coronary event is the leading cause of death among diabetics. These patients have an increased risk of complications after an acute coronary syndrome both during the acute phase and in the post-infarction period. Experimental evidences showed an increased prevalence of atherosclerosis as well as platelet and coagulation abnormalities in patients with diabetes, even after data adjustment for other risk factors. Both hyperglycemia and insulin resistance play a role in the pathogenic link between diabetes and atherosclerosis. Diabetic patients, therefore, could derive a greater benefit from therapies shown to be effective in treating and preventing ischemic heart disease. An aggressive correction of cardiovascular risk factors and accurate risk stratification of patients with diabetes are needed.