The aim of this article is to describe the current status and understanding and the clinical data related to the effects of Tight Glucose Control by Intensive Insulin therapy, TGCIIT, in critically ill patients. Recent prospectively collected data, from one centre, demonstrated decreases of mortality and of various other outcomes in critically ill patients treated with TGCIIT. These results are currently awaiting confirmation, although available data from prospective multi-centre studies do not seem to support the external validity of the beneficial effects of TGCIIT titrated to restore blood glucose between 80 and 110 mg/dl. Also, recent data raised new closely related and relevant issues including the variability of blood glucose, the risks of hypoglycaemia, and the delineation of the categories of patients in whom TGCIIT could bring an actual benefit.