Recent interest in alternative brain fuels (including lactate derived from glucose largely within the brain; refs. notwithstanding, glucose is an obligate metabolic fuel for the brain under physiological conditions .Because the brain cannot synthesize glucose or store substantial amounts as glycogen in astrocytes, the brain requires a virtually continuous supply of glucose from the circulation. Facilitated diffusion of glucose from the blood into the brain is a direct function of the arterial plasma glucose concentration. The rate of blood-to-brain glucose transport exceeds the rate of brain glucose metabolism at normal (or elevated) plasma glucose levels, but it falls and becomes limiting to brain glucose metabolism when arterial glucose concentrations fall to low levels. Thus, hypoglycemia causes brain fuel deprivation and, as a result, functional brain failure.