Myelodysplastic syndrome continues to present a formidable clinical challenge. Despite considerable effort, no therapy apart from allogeneic bone marrow transplantation has been shown to prolong survival. Lack of effective therapy for myelodysplastic syndrome is of further concern given recent reports on the high incidence of myelodysplastic syndrome in patients undergoing intensive chemotherapy and radiation therapy for other malignancies. However, significant strides have been made in the past year toward understanding the molecular pathogenesis of some forms of myelodysplastic syndrome, as well as developing new approaches for therapy of myelodysplastic syndrome. This review highlights recent advances in the molecular genetics of myelodysplastic syndrome, including clonality analysis and identification of genes that are causally implicated in the pathogenesis of myelodysplastic syndrome; results from recent clinical trials for therapy of myelodysplastic syndrome using growth factors, chemotherapy or both; and recent literature on therapy-related myelodysplastic syndrome in intensively treated patients.