Purpose of Review: Treatment-related myelodysplastic syndrome (t-MDS) is a serious complication of cancer treatment. Here we review recent advances in knowledge of the risk factors, pathogenesis, and treatment of t-MDS. Recent Findings: Recent studies have provided important new information regarding genetic risk factors that may predispose individual patients to develop t-MDS after exposure to cytotoxic therapeutic agents and that may be used to predict individuals at enhanced risk for this complication. The role of specific candidate genes associated with commonly involved genetic lesions in the pathogenesis of t-MDS has also been investigated. Finally, factors determining outcomes of transplantation treatment for this disorder have been elucidated. Hematopoietic cell transplantation provides potentially curative therapy for t-MDS, but additional improvements are necessary to improve outcomes. Summary: Improved understanding of genetic risk factors is expected to facilitate early identification of patients at risk for t-MDS, guiding therapeutic decision making, and allowing early application of preventive or therapeutic strategies. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.