Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal disorders of myeloid hematopoietic stem cells affecting about 300,000 people worldwide. Ineffective hematopoiesis and clonal proliferation result in significant cytopenias in affected individuals. Patients are categorized into risk groups (i.e., low, intermediate [1 and 2], and high) based on severity of cytopenias, cytogenetic abnormalities, and the presence of bone marrow blasts. The only potentially curative treatment for MDS is hematopoietic stem cell transplantation, which often is not an option because of advanced age at diagnosis (median age = 76 years). Several alternative treatments to hematopoietic stem cell transplantation show great promise. For low- and intermediate-1-risk MDS, the novel antitumor immunomodulatory agent lenalidomide is approved for patients with del(5q), and two different hypomethylating agents, azacitidine and decitabine, are approved for intermediate-2- and high-risk MDS. Trial results have increased the understanding of these treatments, alone or in combination with other therapies. Effective treatment often requires at least three to six months to achieve a clinical response. In the meantime, or in addition to active therapy, supportive care has a positive effect on quality of life. Greater understanding of the factors affecting MDS treatment options will assist oncology nurses in facilitating the optimal combination of treatment, supportive care, and management of adverse events.