Selecting the most appropriate treatment for patients with myelodysplastic syndromes (MDS) requires careful consideration of several factors. Most patients with MDS are in the 7th or later decade of life and often have comorbid health problems influencing treatment tolerance. Poor-prognosis MDS, as indicated by unfavorable cytogenetics or an increased percentage of myeloblasts, warrants more aggressive interventions than more indolent forms, which might remain stable for many years without treatment. The only curative treatment for MDS is allogeneic stem cell transplantation; however, only a small percentage of patients are candidates for this aggressive treatment. Traditional management for most patients with MDS is supportive care with red blood cell and platelet transfusions or hematopoietic growth factor support and antibiotics for infections. More detailed scrutiny of the processes involved in the MDS phenotype has stimulated investigation into identifying alternate therapeutic options that are effective and better tolerated. Herein, we summarize an array of novel treatments in development for the management of MDS.