Recent developments in our understanding of stem- and progenitor cell differentiation raises hopes that brain damage in chronic neurological diseases may become repaired by systemic or focal transplantation of such cells. In this review the potential of such an approach is discussed, but it is also highlighted that many aspects regarding its feasibility or safety are currently unresolved. Furthermore, recent findings on the pathogenesis of multiple sclerosis lesions indicate that major problems in this disease rather are related to axonal pathology and neurodegeneration rather than to the absence of oligodendrocyte progenitor cells within the lesions. In light of this complex situation, it is concluded that clinical trials of stem- or progenitor cell transplantation in multiple sclerosis are currently premature.