The regional high distribution of D-serine in mammalian central nervous system is consistent with that of N-methyl-D-aspartate receptor. D-serine is synthesized by a glial serine racemase, a novel enzyme converting L- to D-serine in mammalian brain. D-amino acid oxidase (DAO) is a flavoenzyme that catalyzes D-amino acids. D-serine as a glia-derived transmitter not only questions the basic ideas about “neurotransmitter” but also offers a novel way to treat some brain disorders as both over-stimulation and down regulation of NMDA receptors has been implicated in a large number of acute and chronic neurodiseases.