Given the relatively long survival and low rate of progression to AML seen in patients with IPSS Low and INT-1 risk disease, allogeneic transplant is typically reserved for those who fail conservative management with erythropoiesis stimulating agents, G-CSF, hypomethylating agents such as azacitidine or decitabine, lenalidomide, or immune suppression therapy. For patients 60 years of age and younger with advanced MDS (INT-2, High), allogeneic hematopoietic cell transplant is the most appropriate therapy as it prolongs life expectancy. Due to advanced age and significant co-morbidities, allogeneic hematopoietic transplant is not an appropriate treatment modality for a large number of patients with advanced MDS. In addition, stem cell donors are not available for all patients. For patients with advanced MDS, hypomethylating agents or enrollment on clinical trials are both appropriate treatment options given the poor outcomes in this patient population. A phase III open-label, randomized trial of azacitidine versus conventional care regimens in advanced MDS showed superior overall survival for patients treated with azacitidine (24.5 versus 15.0 months, HR 0.58; 95% CI 0.43-0.77). Although decitabine has activity in MDS, it has not been shown to prolong survival in advanced MDS to date. In a phase III study comparing decitabine to supportive care, decitabine showed a superior response rate and delayed the time to the development of AML.