The human brain depends on glucose to fuel all its functions. Although the brain can use other metabolic substrates, and babies’ brains do, glucose is its normal energy source. As the brain stores very little glucose, its proper function depends on a reliable supply from its circulation. If blood glucose concentrations fall too low, then brain malfunction results. But what is the plasma glucose concentration that is ‘too low’? Stephaine Amiel looks into this surprisingly controversial topic.