Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,aswell as the ability to elicit potent anti-tumor effects.However the clinical results for these processes are stillelusive.Greater understanding of NK cell biology,from activating and inhibitory receptor functions to the roleof NK cells in allogeneic transplantation,needs to be appreciated in order to draw out the clinical potential ofNK cells.Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptorsspecific for major histocompatibility complex (MHC) molecules and on activating receptors that have manypotential ligands.The modulation of activating and inhibitory receptors may hold the key to clinical successinvolving NK cells.Pre-clinical studies in mice have shown that different combinations of activating andinhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD),promote engraftment,andprovide superior graft-versus-tumor (GVT) responses.Recent clinical data have shown that the use ofKIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloidleukemia at high risk of relapse.This review will attempt to be a synthesis of current knowledge concerning NKcells,their involvement in BMT,and their use as an immunotherapy for cancer and other hematologicmalignancies.Cellular & Molecular Immunology.2004;1(1):12-21. Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, aswell as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are stillelusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be depent on on inhibitory receptors specific for major histocompatibility complex ( MHC) molecules and on activating receptors that have many potential receptors. The modulation of activating and inhibitory receptors may hold the key to clinical successinvolving NK cells. Pre-clinical studies in mice have shown that different combinations of activating andhibitory receptors on NK cells can reduce graft -versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Central clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse.This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004; 1 (1): 12-21.