The distinct isoenzyme-specific localization of creatine kinase (CK) isoenzymes found recently in brain suggests an important function for CK in brain energetics and points to adaptation of the CK system to the special energy requirements of different neuronal and glial cell types. For example, the presence of brain-type B-CK in Bergmann glial cells and astrocytes is very likely related to the energy requirements for ion homeostasis (K(+)-resorption) in the brain, as well as for metabolite and neurotransmitter trafficking between glial cells and neurons. In contrast, the presence of muscle-type M-CK, found exclusively in Purkinje neurons which also express other muscle-specific proteins, is very likely related to the unique calcium metabolism of these neurons. In addition, the developmentally late appearance of mitochondrial CK (Mi-CK) during brain development indicates an important function for Mi-CK in the oxidative energy metabolism of the brain. The physiological importance of the phosphocreatine circuit fully operating in adult brain has been corroborated by recent data from in vivo 31P-NMR magnetization transfer measurements. Future investigations should concentrate on the possible involvement of CK in diseases of the CNS with altered energy metabolism, aspects of which are also discussed here.