The efficacy of azacitidine, a cytosine nucleoside analog, has been demonstrated in two large phase III trials in myelodysplastic syndromes (MDS) patients, primarily in higher-risk patients. In the Cancer and Leukemia Group B (CALGB) study (lower-and higher-risk MDS patients; n = 191) azacitidine significantly prolonged median time-to-progression to acute myeloid leukemia or death (21 vs 13 months for supportive care; p = 0.007). The AZA-001 trial (Intermediate-2-and High-risk MDS patients; n = 358) showed azacitidine significantly prolonged median overall survival compared with conventional care regimens (24.5 vs 15.0 months; p = 0.0001). These results establish azacitidine as a reference first-line treatment in patients with Intermediate-2-and High-risk MDS who are not immediate candidates for allogeneic stem cell transplantation.