Diabetes mellitus is a potent risk factor for the development of a wide spectrum of cardiovascular (CV) complications. The complex metabolic milieu accompanying diabetes alters blood rheology, the structure of arteries and disrupts the homeostatic functions of the endothelium. These changes act as the substrate for end-organ damage and the occurrence of CV events. In those who develop acute coronary syndromes, patients with diabetes are more likely to die, both in the acute phase and during follow-up. Patients with diabetes are also more likely to suffer from chronic cardiac failure, independently of the presence of large vessel disease, and also more likely to develop stroke, renal failure and peripheral vascular disease. Preventing vascular events is the primary goal of therapy. Optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional CV risk factors to optimize blood glucose, lipid and blood pressure control. Targeting medical therapy to improve plaque stability and diminish platelet hyper-responsiveness reduces the frequency of events associated with atherosclerotic plaque burden. In patients with critical lesions, revascularization strategies, either percutaneous or surgical, will often be necessary to improve symptoms and prevent vascular events. Improved understanding of the vascular biology will be crucial for the development of new therapeutic agents to prevent CV events and improve outcomes in patients with diabetes.