Central fatigue describes circumstances under which strength appears to be limited by the ability of the central nervous system to recruit motoneurones. Central fatigue manifests when the effort to contract skeletal muscles is intense, and thus increases when exercise is performed under stress, as provoked by an unusual environment, and is attenuated following training. Central fatigue is associated not only with reduced strength but also with an inability to maintain contraction. Generation of force, thereby, resembles that developed under the influence of a competitive neuromuscular blocking agent, which mainly affects slow twitch muscle fibres. Central fatigue has not been explained, but the cerebral metabolic response to intense exercise, as to other modalities of cerebral activation, is a reduction in its metabolic ratio, i.e. the ratio between the brain’s uptake of oxygen relative to that of carbohydrate. At rest the cerebral metabolic ratio is close to 6 but during intense whole body exercise it decreases to less than 3, with the uptake of lactate being as important as that of glucose. This apparent inability of the brain to oxidise carbohydrate taken up during activation remains debated with the concomitant uptake of ammonium suggesting that less than 10% of the up to 10 mmol “extra” carbohydrate taken up by the brain is used for formation of amino acids. Accumulation of metabolic intermediates and compartmentalisation of substrate between astrocytes and neurones are avenues that need to be explored considering that breakdown of glycogen in the astrocytes may account for the additional 10 mmol glycosyl units.