Hyperglycemia occurs in patients with diabetes and in nondiabetic patients during acute illness. Epidemiologic and observational studies have demonstrated that hyperglycemia is associated with significant adverse outcomes. Nevertheless, studies evaluating the benefits of normalizing glycemia have produced inconsistent results. For instance, intensive control of hyperglycemia had been shown to provide microvascular benefit in type 1 and type 2 diabetic patients, but its macrovascular benefits had only been clearly demonstrated in type 1 diabetic patients. Moreover, although initial studies in critically ill patients showed decreased morbidity and mortality with tight glycemic control, subsequent studies yielded conflicting results. A series of recent studies provide further insight and show that intensive glycemic control in type 2 diabetic patients does provide macrovascular benefit but is associated with increased risk of hypoglycemia. In the critically ill patient, tight glycemic control could be detrimental; thus, a less aggressive glycemic target of 140 to 180 mg/dL is preferred.