Large amounts of energy are required to maintain the signaling activities of CNS cells. Because of the fine-grained heterogeneity of brain and the rapid changes in energy demand, it has been difficult to monitor rates of energy generation and consumption at the cellular level and even more difficult at the subcellular level. Mechanisms to facilitate energy transfer within cells include the juxtaposition of sites of generation with sites of consumption and the transfer of approximately P by the creatine kinase/creatine phosphate and the adenylate kinase systems. There is evidence that glycolysis is separated from oxidative metabolism at some sites with lactate becoming an important substrate. Carbonic anhydrase may play a role in buffering activity-induced increases in lactic acid. Relatively little energy is used for 'vegetative' processes. The great majority is used for signaling processes, particularly Na(+) transport. The brain has very small energy reserves, and the margin of safety between the energy that can be generated and the energy required for maximum activity is also small. It seems probable that the supply of energy may impose a limit on the activity of a neuron under normal conditions. A number of mechanisms have evolved to reduce activity when energy levels are diminished.