Anemia is the most common cytopenia associated with myelodysplastic syndromes (MDS). Current management relies on frequent red blood cell (RBC) transfusions and erythroid growth factors to alleviate symptoms. However, the dependence of patients with MDS on repeated RBC transfusions often results in significant clinical and economic consequences, poorer outcomes, and diminished health-related quality of life. In addition, the intensity and duration of RBC transfusion dependence can influence responses to treatment after disease progression. Erythropoietic growth factors may alleviate the need for RBC transfusions in some patients with MDS, although only a minority of patients experience responses. Emerging treatment strategies to reduce or eliminate the need for RBC transfusions in patients with MDS include immunomodulating drugs, immunosuppressive therapy, and differentiating agents. The immunomodulating drug lenalidomide in patients who have MDS with 5q deletion is unique among emerging approaches, in that cytogenetic remitting activity and durable erythroid responses have been achieved. Newer treatments have the potential to improve the care of patients with MDS by alleviating the clinical, economic, and quality-of-life consequences of long-term RBC transfusion dependence. Cancer 2006. © 2006 American Cancer Society.