Leukemia is a malignancy of the bone marrow and blood resulting from the abnormal differentiation of hematopoietic stem cells (HSCs). There are four main types of leukemia including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). While chemotherapy and radiation have been conventional forms of treatment for leukemia, these therapies increase infection susceptibility, adverse side effects and immune cell inactivation. Immunotherapies are becoming promising treatment options for leukemia, with natural killer (NK) cell-mediated therapy providing a specific direction of interest. The role of NK cells is critical for cancer cell elimination as these immune cells are the first line of defense against cancer proliferation and are involved in both recognition and cytolysis of rapidly dividing and abnormal cell populations. NK cells possess various activating and inhibitory receptors, which regulate NK cell function, signaling either inhibition and continued surveillance, or activation and subsequent cytotoxic activity. In this review, we describe NK cells and NK cell receptors, functional impairment of NK cells in leukemia, NK cell immunotherapies currently under investigation, including monoclonal antibodies (mAbs), adoptive transfer, chimeric antigen receptor-NKs (CAR-NKs), bi-specific/tri-specific killer engagers (BiKEs/TriKEs) and future potential targets of NK cell-based immunotherapy for leukemia.