The management of patients with myelodysplasia (MDS) can be quite complex and varies according to both the clinical manifestations in individual patients as well as complicating medical conditions. Allogeneic stem cell transplantation is the only curative treatment, but because of the older age of the patient population must be applied selectively, particularly in those with lower risk MDS as well as in patients whose clinical course is more frankly "preleukemic." Issues pertinent to the use of 5-azacytidine, decitabine and lenalidomide in patients with both higher and lower International Prognostic Staging System (IPSS) stage disease are discussed.