Diabetes mellitus is a heterogeneous disorder. About 80% of the patients with this disease are categorized as having non-insulin-dependent diabetes mellitus, a disorder resulting from varied degrees of insulin resistance and impaired insulin secretion; the causes for these abnormalities are unknown. The remaining 15 to 20% of patients have insulin-dependent diabetes mellitus, a disorder caused by the destruction of insulin-producing endocrine cells within the pancreas and currently considered to be the result of an autoimmune process. During the course of both types of diabetes mellitus, the so-called long-term complications of diabetes invariably occur to some extent in all patients. These complications include retinopathy, nephropathy, neuropathy, and premature atherosclerosis. The molecular basis for these complications is not completely understood, but recent evidence obtained from both experiments in animals and prospective clinical studies indicates that metabolic derangements associated with poor glycemic control are a major determinant of the frequency and severity of these complications. Such evidence is the rationale for current attempts to maintain near-normal glycemia in patients with diabetes mellitus.