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The prognosis of elderly patients with acute myeloid leukemia (AML) is poor. Intensive chemotherapy with the combination of cytarabine and anthracyclines is typically used as the first-line treatment in the elderly with newly diagnosed AML who are able to tolerate this regimen. Unfortunately, many patients are refractory to this treatment approach. The role of hypomethylating agents in the treatment of elderly patients with refractory AML has not been clearly defined. Therefore, we conducted a focused literature review to assess the role of hypomethylating agents in elderly patients with refractory AML. In addition, we present a case report of a patient with refractory AML, who was subsequently treated with azacytidine and showed an immediate response after one treatment cycle. He then proceeded to undergo nine more cycles. Ten months after the start of treatment with azacytidine, he remains in complete remission with incomplete hematologic recovery. Given the positive results noted in multiple retrospective studies and in the presented case report, large-scale, prospective studies are needed to further define the role of hypomethylating agents in the treatment of elderly patients with refractory AML.