Chester et al. briefly describe NK-cell–tumor interactions and the three most important mechanisms of how NK cells kill target cells, i.e., natural killing, antibody-dependent cell-mediated cytotoxicity (ADCC), and death receptor-induced apoptosis, and follow with a description of the best studied activating and inhibitory receptors involved in tumor cell recognition, along with the ability of agonistic monoclonal antibodies (mAbs) specific for costimulatory molecules, such as CD137 and OX40. Here, TNFRSF9 is linked to neoplasm.