Glycogen is located exclusively in astrocytes, but not axons, in the optic nerve, a central white matter tract, and provides glycogen-derived lactate to axons during times of increased energy demand and restricted glucose supply. In the sciatic nerve, a peripheral nerve trunk, glycogen is located in Schwann cells, where it possesses the intriguing feature of only supporting conduction in large myelinated A fibres; the unmyelinated C fibres do not benefit from its presence. This highlights intriguing similarities and differences between the role of glycogen in the central and peripheral nervous systems. Although glucose is unanimously agreed as the predominant energy support in the nervous system, the efficiency with which other substrates support function can provide insight into tissue-specific metabolic preferences. In the optic nerve fructose supports conduction of smaller diameter axons due to the presence of fructokinase expression; larger diameter axons lack this enzyme. In the sciatic nerve the situation is more complicated due to fibre subtype differences. The C fibres of the sciatic nerve appear to act in a similar manner to optic nerve axons, whereby they take up and directly metabolise fructose, whereas the A fibres utilise Schwann cell glycogen and fructose-derived lactate. The signalling mechanism by which neural elements alert glial cells is likely to be K⁺. An inevitable consequence of firing activity in all axons is an increase in interstitial [K⁺]. Glial cells are exquisitely sensitive to K⁺, thus are primed to act as sensitive detectors of neuronal activity and respond accordingly. An appealing theory in the central nervous system (CNS) proposes activity evoked interstitial [K⁺] elevations stimulate astrocytic soluble adenylyl cyclase activity, which triggers glycogen breakdown and lactate release for neuronal uptake: whether this applies to the peripheral nervous system (PNS) remains tantalisingly unresolved.