Carbohydrates present the most accessible energy source for many tissues. Glucose is the only fuel that can be respired anaerobically, for example by the Type 2 skeletal muscle fibre during intensive exercise or by the erythrocyte which has no mitochondria. It is also the preferred fuel for the central nervous system (CNS). The brain has a sustained high energy requirement to allow continuous ion pumping and maintenance of membrane potentials, and accounts for approximately 20% of resting energy expenditure in the fat-free mass of the adult. In the fed state, the brain consumes only glucose, oxidising it to supply 100% of its energy requirement, accounting for about 120 g glucose per day in the adult. In the starving state, the brain may reduce its glucose requirement by up to 75% by consumption of ketone bodies but the remaining 25% of its energy must always come from glucose. Lipoproteins do not cross the blood-brain barrier, depriving the brain of fat as an oxidative fuel. The dependence of the CNS on glucose justifies the complexities of glucose homeostatic mechanisms designed to maintain availability of this substrate through the bloodstream and explains the potentially coma-inducing consequences of poorly controlled diabetes or excessive alcohol consumption.