The treatment of myelodysplastic syndromes (MDS) involves a complex algorithm that depends on multiple factors, including symptoms, performance status, and severity of disease. Current therapies are aimed at promoting hematopoiesis, inhibiting apoptosis, and reducing the risk of transformation to acute myeloid leukemia. Although there is no cure for MDS outside of allogeneic stem cell transplantation, goals of treatment include improvement of peripheral blood cytopenias, reduction of transfusions, improvement of the quality of life, and prolongation of survival. Patients with lower-risk MDS are often asymptomatic and can be monitored for long periods without therapeutic intervention. Anemia, the most common symptomatic cytopenia, warrants treatment in an attempt to eliminate transfusion dependence. This article reviews current treatment strategies for lower-risk MDS and examines the data for selected novel agents that are available or are being developed for the treatment of this disease.