Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Although most patients achieve complete remission (CR) after chemotherapy, the majority suffer from subsequent leukemic relapse, which is associated with poor long-term survival. Thus, new therapies to maintain CR are highly warranted. After the completion of chemotherapy, AML patients have a minimal burden of leukemic cells, which are reportedly susceptible to cytotoxic lymphocytes such as NK cells and T cells. A therapy that boosts the function of these effector cells therefore has the potential to eradicate the malignant clone in AML and prevent relapse, Here, we briefly review the literature on the role of the immune system in AML and introduce the rationale for the use of histamine dihydrochloride (HDC) in conjuction with low-dose IL-2 as relapse-preventive immunotherapy for this disease.