Natural killer (NK) cells are cytotoxic against a variety of transformed and virus-infected cells. Cytotoxicity of NK cells is regulated through complex interactions between receptors expressed on NK surface and their cognate ligands expressed on the surface of target cells. A large body of data supports the concept that NK are key players of immune surveillance against cancer, and NK cell based immunotherapy has been proved to be feasible and effective. Allogeneic NK cell infusion, in nontransplant recipients with malignant disorders, is associated with a modest but of a short-term duration antitumor effect. The major limitation of allogeneic-NK therapy is the inevitable rejection of allogeneic effectors and the termination of antitumor activity. Allogeneic NK cells are not rejected by the host if infused after stem cell transplantation from the same donor. Although the existing data are limited, allogeneic-NK immunotherapy is much more effective if performed after haploidentical stem cell transplantation. Future trials should address this issue.