Many patients with type 2 diabetes require insulin therapy for improved glycemic control after beta-cell failure. However, many physicians are reluctant to institute insulin therapy in type 2 diabetes for fear of accelerating atherosclerosis. The epidemiological evidence is reasonably sound that hyperinsulinism correlates with increased cardiovascular disease in nondiabetic people and those with early type 2 diabetes. It is much less clear, however, that insulin concentration plays a negative role when less well controlled diabetes is considered. The data are more consistent, in fact, with the glucose hypothesis, i.e., that hyperglycemia is a risk factor, although the magnitude of the glucose effect is not well defined. Certainly, the dysmetabolism associated with poor glycemic control could increase the risk of macrovascular events through well-known mechanisms. There is direct evidence that insulin therapy can reduce the risk of macrovascular events by improving glycemic control and diabetes-associated dyslipidemias, although the beneficial effects may be significantly compromised by excessive weight gain. Insulin therapy does not appear to induce hypertension independent of changes in body weight. It is concluded that optimal glycemic control confers a known benefit and can only be achieved with insulin therapy in some people with type 2 diabetes. In these circumstances, the use of insulin has a net benefit on cardiovascular risk, mediated primarily through improvement in dyslipidemia and glycemia itself.