High-risk myelodysplastic syndromes present a poor prognosis, with survivals of close to only 1 year. The use of azacitidine, a DNA methyltransferase inhibitor, in this group of patients has transformed this grey image, with a demonstrated improvement in survival. Responses to survival are attained in a progressive manner, providing that the drug is used continually. This requires a good control of the adverse effects of the drug, which are primarily in the first cycles of treatment. The hematological adverse effects can be handled with transfusions and growth factors. The nonhematological adverse effects can be prevented with the use of antiemetics and a good technique of drug administration.