NO (nitric oxide) participates in a considerable number of physiological functions. At the biochemical level, most of its actions can be ascribed to its ability to bind, and activate, soluble guanylate cyclase. However, mounting evidence now strongly suggests that the NO-mediated inhibition of cytochrome c oxidase, the terminal complex of the mitochondrial respiratory chain, may be a further step of a cell signalling process involved in the regulation of important cellular functions. In most cells, including neurons and astrocytes, NO reversibly, and irreversibly, modulates O(2) consumption, a phenomenon through which NO signals certain pathways relevant for neuronal survival. Here, we propose that besides the control of mitochondrial bioenergetics, NO finely modulates the balance between glucose consumption through the glycolytic pathway and the pentose phosphate pathway in neurons. This may have implications for our understanding of the mechanisms of neurodegeneration due to oxidative and nitrosative stress.