A considerable level of D-serine (a free D-amino acid) was discovered, surprisingly, in the mammalian brain in the early 1990s. Since then, D-serine has been considered to be a co-agonist of glutamate at the glycine site of NMDA receptors. D-serine is synthetized by racemization of L-serine in most neural and non-neural cells, and modulates a variety of physiological functions in mammals. In addition to the central nervous system, NMDA receptors have an important function in the modulation of physiological processes in peripheral tissues. Thus, investigations on the functions of D-serine in the peripheral nervous system, as well as the visceral organs, have gained attention in recent years. In this review we summarize the current knowledge on the role of D-serine in the kidneys, skeletal system, skin as well as on the non-adrenergic, non-cholinergic transmission within the autonomic nervous system.