The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders that manifest as bone marrow failure with the risk of life threatening infections and bleeding. A third of these patients may transform to acute leukemia. Age and co-morbidities have limited treatment in the majority to supportive care with a minority of patients eligible for the only curative modality to date, allogeneic stem cell transplantation. The advent of targeted therapy has increased the repertoire of therapeutic options. In particular the methyl transferase inhibitor 5 Azacytidine, that targets epigenetic changes in MDS, has been shown to be effective in up to 60% of patients in a Phase III randomized controlled trial comparing it with best supportive care and has been licensed by the US Food and Drug Administration for use in all subtypes of MDS. It has been shown to prolong time to leukemic transformation (21 vs 12 months with 3% transforming to leukemia p=0.0001) and is the only disease-modifying drug. Patients with monosomy 7, trisomy 8, and diploid chromosomes appear to particularly benefit with the former deriving sustained remissions. As an outpatient therapy, with an acceptable side effect profile, treatment with Azacytidine needs to be considered in all MDS patients who are eligible for treatment.