Diseases of the brain and spinal cord are especially daunting challenges for cell-based strategies of repair, given the multiplicity of cell types within the adult central nervous system, and the precision with which they must interact in both space and time. Nonetheless, a number of diseases are especially appropriate for cell-based therapy, in particular those in which single phenotypes are lost. Foremost among these are the disorders of myelin, in which oligodendrocytes are the specific and often sole victims of the underlying disease process. These include not only the vascular, traumatic, and inflammatory demyelinations of adulthood, but also the congenital and childhood dysmyelinating syndromes of the pediatric leukodystrophies. These congenital disorders of myelin formation and maintenance may present especially compelling targets for cell-based neurological therapy.