Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation.