Maintaining plasma glucose concentration is a critical requirement for the body, making the detection of blood glucose by the nervous system essential. The reason generally given is that glucose is the main source of energy for living cells. In fact, other reasons make that glucose is so crucial. Glucose feeds two non-oxidative metabolic pathways, glycolysis and the pentose pathway, which allow the synthesis of molecules essential for cell survival and division, such as amino acids or nucleotides. The purpose of this review is to argue this statement and discuss the processes of glucose sensing by the central and peripheral nervous systems.