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Natural killer (NK) cell-based immunotherapy has the potential to improve outcomes for patients with AML. Summary: Recent preclinical studies and early-stage clinical trials aim to enhance the intrinsic anti-leukemic properties of NK cells by selectively targeting AML cells with chimeric antigen receptors (CARs). Furthermore, NK and CAR-NK cells can be combined with other therapeutic modalities or engineered further to overcome the immunosuppressive microenvironment, and treatment resistance of AML blasts and leukemia-initiating cells (LIC). Key Messages: In this review, we summarize preclinical studies with cytokine-stimulated or genetically engineered NK cells derived from different cell sources for the treatment of AML and their translation into early-phase clinical trials. 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