The relationship between abnormal circulating glucose levels and the development of long-term diabetic complications became apparent soon after the introduction of insulin 70 years ago and the avoidance of early death due to ketoacidosis. Classic observational studies by Pirart described the relationship between increased glycosuria and the ultimate development of diabetic retinopathy, nephropathy, and neuropathy. Nonetheless, it required the findings of randomized, controlled clinical trials to finally and definitively establish the relationship between glucose control and microvascular diabetic complications. With the publication of the Diabetes Control and Complications Trial, the Kumomoto Trial, and the United Kingdom Prospective Diabetes Study, the impact of glycemic control in the development of microvascular complications was confirmed. Our understanding of the pathophysiology of diabetes--particularly, the dysmetabolic changes seen in type 2 diabetes--includes abnormalities in lipid metabolism, fuel flux, and endothelial function. Diabetes control, therefore, can no longer be viewed exclusively as glucose management. Rather, a more global approach is necessary to minimize risks of both microvascular and macrovascular complications. This article explores data supporting a variety of interventions that have been shown to reduce morbidity and mortality associated with long-standing diabetes mellitus. In addition to acknowledging the relationship between complications and diabetic metabolic abnormalities, this article presents a health economics perspective by examining the cost-effectiveness and health utility of these interventions.