 Acute myeloid leukemia, or AML, is a form of blood cancer that compromises healthy self-production. Patients with AML are gently treated with intensive chemotherapy. However, while advances in treatments have led to improvements in outcomes for younger patients with AML, little progress has been made in improving outcomes for patients older than 60. That's especially true for patients who are, for one reason or another, not eligible for standard treatment with chemotherapy. A review of clinical and real-world studies suggests that the use of hypermethylating agent decytobene can be a valuable treatment option for this at-risk population. Decytobene works by inhibiting the methylation of DNA. This disruption of methylation can make way for anti-tumor genes to be reignited and mounted offence against cancer cells. In 2012, a Phase 3 registration trial was published in which the effects of decytobene in 485 older patients was examined. Patients were aged 65 or older, had newly diagnosed or secondary AML, and were not eligible to receive standard chemotherapy. These patients were divided into a treatment group receiving decytobene, and a control group receiving the physician's treatment of choice of citerobene, or supportive care alone. Patients in the treatment group received decytobene by one hour infusion daily for five consecutive days every four weeks. The results of the trial were favorable for the group receiving decytobene, the median overall survival for these patients was 7.7 months, 2.7 months longer than the overall survival of patients in the control group. Similar differences in favor of the decytobene group were observed for event-free survival, progression-free survival, and clinical response based on complete remission. Real-world studies from Belgium, Italy, and the United States confirmed the benefits of decytobene for overall survival in AML patients not eligible to receive chemotherapy. Explorative analyses from within these trials also showed more pronounced positive value in terms of extended survival rates in patients in complete remission or treated for more than four cycles. Furthermore, data from both the registration trial and real-world studies showed that the toxicity associated with decytobene is relatively mild, and that adverse events are manageable with no additional adverse events reported in the real-world studies relative to the more controlled clinical trials. The findings also suggest benefit for patients with specific aberrations in their chromosomal profile, namely those who are positive for a monosomal career type. Furthermore, decytobene may partially overcome the adverse prognostic effect of a TP53 mutation. In conclusion, although more work is needed to identify AML patients who are most likely to benefit from decytobene, the clinical and real-world evidence gathered to date showed clearly the survival improvements possible in patients typically facing poor prognoses.