Natural killer (NK) cells express a set of activating and inhibitory receptors which, after interaction with their ligands, determine whether or not the target cell will be lysed. Many studies have clearly demonstrated that NK cells have the capacity to lyse stressed cells (such as tumor or virally-infected cells). However, NK cells that infiltrate tumors usually exhibit phenotypic and functional defects. In this issue of the European Journal of Immunology, Vacca et al. [Eur. J. Immunol. 2013. 43: 550‒561] show that NK cells in pleural effusions of primary and metastatic tumors of various origins are not anergic, possibly because the downregulation of activating receptors and the upregulation of inhibitory receptors does not occur, as previously reported for tumor NK cells. Another major finding of this study is the capacity of these pleural NK cells to respond to IL-2 stimulation, as the authors demonstrate that pleural NK cells stimulated by IL-2 in long-term culture acquire the capacity to lyse autologous tumor cells isolated from pleural effusions. These results support the treatment of primary or metastatic pleural tumors with IL-2 or other innovative strategies currently being developed to stimulate NK cells in cancer patients as discussed in this Commentary.