The mechanisms determining the fate of Schwann cells during disease and injury of the adult mammalian peripheral nervous system (PNS) are becoming defined by current advances in molecular neurobiology. It is now apparent that the molecular pathways which regulate the production of the mature myelinating Schwann cell during development may also apply to degenerative and regenerative mechanisms following PNS disease. This review outlines neurobiological responses of Schwann cells during development, injury and disease in order to define the molecular pathways which regulate these crucial events. These mechanisms have implications for our attempts to intervene pharmacologically during pathologies of the PNS.