Myelodysplastic syndromes (MDS) are a group of disorders characterized by progressive cytopenias and transformation to acute leukemia. Over the last four years, we have experienced a revolution in the treatment of MDS. Three drugs were approved in the U.S. Two of them, 5-azacitidine and 5-aza-2'-deoxycitidine, induce DNA hypomethylation. The third agent, lenalidomide, is a thalidomide analogue with significant activity in a subset of patients with low-risk MDS, anemia and chromosome 5 alterations. Several other agents are being evaluated in MDS. In this short review, we will summarize our current approach to the therapy of patients with MDS.