Although transplantation of myelin-forming cells into the central nervous system (CNS) has recently attracted much attention as a potential therapy for repairing persistent demyelination found in the demyelinating diseases such as multiple sclerosis and the leukodystrophies, it is worth remembering that the technique was originally conceived of as an experimental technique for manipulating in vivo environments to study interactions between different cell types in either repair or development. It is in this capacity that the technique is still predominantly used. Nevertheless, information, both technical and biological, that the continued use of the technique yields also often provides material for assessing the feasibility of glial cell transplantation as a therapeutic procedure. In this article, we describe some of the guiding principles of transplantation of myelinogenic cells into the mammalian CNS, focusing initially on the recipient environment and then considering the donor material. The division of the discussion into recipient and donor is one of convenience since in reality the interactions between the two cannot be considered in isolation.