This article summarises the 3 probable reasons why hydrogen-rich fatty acids are used only poorly as fuel in the brain: (1) ATP generation linked to β-oxidation of fatty acids requires more oxygen than glucose, therefore increasing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids produces superoxide, which, together with poor anti-oxidative defence in neurons, causes severe oxidative stress; (3) the rate of ATP generation from adipose tissue-derived fatty acids is slower than using blood glucose as fuel. The authors conjecture that the disadvantages associated with using fatty acids as fuel have created evolutionary pressure favouring glucose oxidation in the brain.