The myelodysplastic syndromes are clonal hematopoietic disorders for which hematopoietic stem cell transplantation remains the only curative therapy. The timing of transplantation, methods of disease risk stratification, patient selection, pretransplantation therapies, and preparative regimens have evolved over the years, resulting in increasing disease-free survival. In recent years, alternative donor sources have been demonstrated to be a viable alternative to traditional sibling and matched unrelated donor stem cell sources. Efforts at transplantation regimen development continue with the aim of maximizing the chances of cure with minimal toxicity and improved quality of life. Integrating new knowledge regarding disease biology will be critical to continue to improve the success of hematopoietic stem cell transplantation. Exciting areas of ongoing research that may lead to reductions in posttransplantation relapse rate include posttransplantation therapies such as DNA methyltransferase inhibitors, vaccine strategies, and donor lymphocyte infusions to enhance the GVL effect.