The management strategy for patients with myelodysplastic syndromes (MDS) has evolved from sole reliance on supportive measures to active treatment guided by disease risks. Recent progress in understanding the molecular pathogenesis of MDS has accelerated the discovery of new therapeutic targets, and consequently launched the development of several novel therapeutics that are currently in varied stages of clinical testing. One such agent is lenalidomide, which has shown remarkable effectiveness in the cytogenetically defined subset of MDS with the chromosome 5q31 deletion. The advent of new and effective targeted therapeutics may beneficially affect outcomes of an ever-increasing number of patients with MDS. This discussion summarizes the preliminary results of selected novel therapeutics.