Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenia and by increased progression to acute myelocytic leukemia (AML). With the exception of allogeneic stem cell transplantation, there is generally no curative treatment for these disorders. As the contribution of diverse pathologic processes to ineffective hematopoiesis in MDS continues to be clarified, promising new avenues for treatment are being identified. Agents that interact with newly defined biologic targets and that are under investigation include arsenic trioxide, DNA methylation inhibitors, farnesyl transferase inhibitors, thalidomide, immunomodulating agents, and histone deacetylase inhibitors.