Hyperglycemia, a common finding in critically ill patients, is linked to poor outcomes in multiple conditions. The Leuven I study published in 2001 was the first evaluation of intensive insulin therapy, and the 3.4% absolute reduction in mortality in a single-center surgical intensive care unit led to widespread endorsement of the therapy. In a subsequent study in a medical intensive care unit, reduction in mortality was not significant. Two multicenter studies were stopped early because of significantly higher rates of hypoglycemia in the patients receiving intensive insulin therapy. The episodes of hypoglycemia were linked to increased mortality. In the largest prospective study conducted to date, mortality was significantly higher (P = .02) in patients who had intensive therapy (27.5%) than in control patients (24.9%). Thus, after years of research, intensive insulin therapy does not appear to convey the original benefit in all critically ill patients. Several organizations have proposed alternative blood glucose targets, such as 140 to 180 mg/dL, to both provide glycemic control and reduce the opportunity for hypoglycemic episodes.