Severe and transfusion-dependent anemia is a major symptom for patients with myelodysplastic syndromes (MDSs). Recent translational research studies have improved treatment approaches for these patients and contributed to our understanding of the pathophysiology of MDSs. For example, the response to antithymoglobulin treatment in certain patients with refractory anemia has elucidated potential immune mechanisms underlying bone marrow failure, whereas the observed effects of erythropoietin with or without granulocyte colony-stimulating factor in other low-risk patients have offered insights into the role of mitochondria-mediated erythroid apoptosis in MDS-related anemia. Current research is aimed at defining the role for other potential pathogenetic mechanisms in the development of MDS. Such studies may lead to individually tailored therapy for MDS patients based on a detailed analysis of the role of different contributing mechanisms to the origins of their disease.