The effects of valproate on brain energy and lipid metabolism is reviewed. Increasing evidence suggests that valproate uses the monocarboxylic acid carrier in order to cross the blood brain barrier (BBB) and the neural cell plasma membranes. The uptake of valproate into the brain through this mechanism would compete with the uptake of energy precursors, such as the monocarboxylic acids 3-hydroxybutyrate, lactate or pyruvate and with some amino acids, but not with glucose. This could impair brain fuel utilization, specially during the neonatal period or childhood, when lactate or 3-hydroxybutyrate furnishes alternative substrates to glucose for the brain. It is concluded that valproate interference with energy metabolism may have implications for the therapeutic action of the drug, stressing the possibility that valproate-mediated alterations in brain lipid synthesis may contribute to the pharmacological action of the drug.