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Myelodysplastic syndrome (MDS) is a stem cell disorder, and hematopoietic stem cell transplantation is currently the only therapeutic modality that is potentially curative. Among patients with less advanced MDS (5% marrow blasts), 3-year survivals of 65-70% are achievable with HLA-identical related and HLA-matched unrelated donors. The overall probability of disease recurrence in these patients is5%. Among patients with advanced disease (/=5% marrow blasts), about 35-45% and 25-30%, respectively, are surviving in remission after transplantation from a related or from an unrelated donor; the incidence of post-transplant relapse is 10-35%. The criteria proposed by the International Prognostic Scoring System (IPSS) derived from non-transplanted patients, also predict survival following transplantation. The development of new conditioning regimens has permitted successful hematopoietic stem cell transplants even in patients more than 60 years of age. Improved survival with transplants from unrelated volunteer donors may, in part, reflect selection of donors on the basis of high resolution (allele-level) HLA typing. Autologous stem cell transplantation may be beneficial for selected patients who have obtained a complete remission with conventional chemotherapy. Treatment-related morbidity and mortality, in particular after allogeneic transplantation, remain challenges that need to be addressed with innovative approaches.