During the past decade, in which the seminal studies have been published, a series of investigations into glucose homeostasis and insulin therapy in the critically ill have also been reported. This chapter addresses the risks associated with hyperglycaemia, the implementation, efficacy and safety of protocols for tight glucose control (TGC) using intensive insulin therapy (IIT), and the measurement of blood glucose in the critically ill. Stress hyperglycaemia is at least as detrimental as hyperglycaemia with prior diabetes mellitus, which may be associated with fewer risks. The first report on IIT for TGC in critically ill patients was published in 2001 from Leuven. The symptoms of hypoglycaemia are confusion, coma, restlessness and seizures. Frequent blood glucose measurements are needed for implementing safe IIT which warrant accurate point-of-care systems in the intensive care unit (ICU), since laboratory measurements are too slow.