For patients with diabetes mellitus (DM), chronic complications can be devastating. Cardiovascular illness, the major cause of morbidity and mortality among these patients, encompasses macrovascular disease, with heart attacks, strokes, and gangrene; and microvascular disease, with retinopathy, nephropathy, and neuropathy (somatic and autonomic). Macrovascular events occur earlier in individuals with DM than in people without DM, and the underlying pathologies are often more diffuse and severe. Diabetic arteriopathy, which encompasses endothelial dysfunction, inflammation, hypercoagulability, changes in blood flow, and platelet abnormalities, contributes to the early evolution of these events. Efforts are under way to determine interventions that may have the potential to prevent or halt the complications of DM. Tight glucose and blood pressure (BP) control is known to improve the vascular status of patients with DM by varying degrees. Use of anti-inflammatory drugs and lowering low-density lipoprotein cholesterol (LDL-C) levels are also useful. An emerging understanding of the importance of small, dense LDL-C and the anti-inflammatory effects of statins has provided new algorithms for primary prevention of macrovascular disease. Antiplatelet agents have also been shown to be effective in the secondary prevention of cardiovascular events. In the ideal world every risk factor would be addressed and each person with DM would have excellent glycemic control, low to normal BP, and a low LDL level, and would be taking an angiotensin-converting enzyme (ACE) inhibitor, together with a statin, aspirin, and clopidogrel. Under these near-perfect conditions, the emerging epidemic of macrovascular disease could be contained. Microvascular disease, however, is a consequence of hyperglycemia. For every 1% reduction in glycosylated hemoglobin it is possible to achieve a 22% to 35% reduction in the microvascular complications. BP control is vital and the liberal use of ACE inhibitors and angiotensin receptor blockers to slow the progression of renal disease should drastically reduce the incidence of blindness, dialysis, and amputations. This article provides an overview of prevention of macrovascular disease such as stroke, myocardial infarction, and peripheral arterial disease and microvascular complications such as retinopathy, nephropathy, and neuropathy in patients with DM.