Treatment of myelin loss is particularly suited to therapeutic strategies based on cell replacement. Demyelination represents a defined and functionally debilitating deficit, and remyelination can be accomplished by supplying regions of demyelination with myelinogenic cell populations. Clinical interest in stem cells as a source of myelinogenic cells arises from their ability to provide an apparently unlimited cell supply for transplantation, and from recent demonstrations that they can be directed to myelinogenic phenotypes with high purity. Here, I present the emerging perspective that stem-cell-mediated remyelination of the adult CNS is a viable therapeutic strategy, and discuss the challenges to remyelination posed by the environment of acute and chronic injuries.