The application of neural stem cell transplantation for cellular repair of lesions of the brain and spinal cord appears to have much greater promise than bone marrow transplantation, viral-mediated gene therapy, or systemic enzyme replacement. The initial approach for treatment of Parkinson’s disease by transfer of dopamine-producing cells provides a prototype for cell transplantation therapy that can be extended to the use of multipotent neural stem cells, which not only have the ability to self-renew and to differentiate into cells of all glial and neuronal lineages, but also can migrate to areas of CNS disease or injury. How transplanted cells and injured/diseased brain communicate with each other in what appears to be directed migration and differentiation is a subject of current investigation. The abililty to isolate and culture cells in vitro that have the migration and differentiation properties of neural stem cells is a major advance in obtaining cells for transplantation therapy. Such cells are relative easy to inject into the ventricles, migrate across the blood—brain barrier, and integrate as different CNS cell type into damaged brain, yet do not give rise to inappropriate cell type or neoplasms. In some proof-of-principle experimental models, transplanted neural stem cells have been used to treat a mouse model of neurogenic lysosomal storage disease, mutant mice with congenital anatomic abnormalities, myelination disorders, hypoxic—ischemic injury, amyloid plaques, and brain tumors by delivery of oncolysis-promoting cytosine deaminase.