The considerable enthusiasm for CAR-T cells to treat malignancies based on the initial impressive results in advanced blood cancers, has been somewhat tempered by their limited efficacy in targeting solid tumors. Waiting in the wings, however is NK cell therapy, now actively emerging as an alternative cancer treatment. Investigation of autologous NK cells has given way to allogeneic sources of the cells. These include permanent NK cells lines, originally derived from patients with NK malignancies, which continue to be explored for their advantages including ready availability as an off-the-shelf cell therapy product, reliable cytotoxicity potency and relative ease of gene modification to improve safety, targeting and efficacy. In this presentation we will discuss the biology of NK cell lines and present an update of a clinical trial of NK-92 in patients with relapsed/refractory hematological malignancies. Strategies to engineer the cells to incorporate safety elements, improve antibody dependent cell mediated cytotoxicity and enhance cancer cell targeting with suitable CARs, especially for solid tumors, will be outlined. We will also discuss how these studies may provide insights into the generation of more effective NK cell products derived from induced pluripotent stem cells [iPSCs].