The brain's energy metabolism is considered to be completely aerobic, with glucose as the major energy substrate for neurons during both rest and activation. This view has now been challenged, as other energy metabolites are shown to play a more important role in the brain's energy metabolism. During development of the brain both lactate and ketone bodies are used as energy substrates. Lactate and ketone bodies are shown to be important energy metabolites in situations of starvation, hypoglycemia and diabetes. During intense physical activity the brain uses lactate from the circulating blood. Lactate and other monocarboxylates cross cell membranes by interaction with specific proteins; the monocarboxylate transporters (MCTs). MCTs are trans-membrane proteins that facilitate cotransport of a monocarboxylate ion with a proton. Whether the transport goes in or out of a brain cell depends on the concentration gradient for the monocarboxylates and the pH-gradient. The brain has been shown to express three different MCTs: MCT1, MCT2 and MCT4. MCT1 is expressed in astrocytes and in microvessel endothelial cells, whilst MCT2 is concentrated in neurons and MCT4 is preferentially expressed in astrocytes. Neurons are considered to be the lactate consuming cells whereas astrocytes are the lactate producers. Lactate may be an important energy substrate for neurons, e.g. in tissue surviving ischemia.