<p>Acute leukemia represents a significant therapeutic challenge, necessitating the development of innovative approaches to improve the clinical outcomes of patients. Immunotherapies have become a mainstay in the treatment of acute leukemia. Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a well-established and efficacious procedure. Over time, a number of therapeutic approaches have emerged as promising strategies for achieving durable remission and have transformed the treatment of leukemia. Among the efficient immune cells engaged against leukemia, natural killer (NK) cells are innate cytotoxic cells that do not require antigenic specificity to exert their cytotoxic function. The potential of NK cells as a treatment for leukemic patients is emerging as a promising approach. They are capable of distinguishing between healthy and leukemic cells in a natural manner because of the sophisticated equilibrium between their numerous inhibitory and activating receptors. In recent years, NK cells have been found to be far more complex than expected. Indeed, the NK repertoire exhibits a remarkably high degree of phenotypic diversity, which is closely linked to the extensive polymorphism of immunogenetic KIR and HLA class I markers. It has been demonstrated that not all NK cells possess the same functional profile and that they respond to functional education mediated by these KIR-HLA molecular interactions. This review offers insights into the knowledge of NK cell diversity, with the goal of leveraging NK cell heterogeneity for the development of NK cell-based immunotherapies for acute leukemia.</p>