Natural killer (NK) cells and dendritic cells (DCs) are two types of specialized cell of the innate immune system, the reciprocal interaction of which results in a potent, activating cross-talk. For example, DCs can prime resting NK cells, which, in turn, after activation, might induce DC maturation. However, NK cells negatively regulate the function of DCs also by killing immature DCs in peripheral tissues. Moreover, a subset of NK cells, after migration to secondary lymphoid tissues, might have a role in the editing of mature DCs based on the selective killing of mature DCs that do not express optimal surface densities of MHC class I molecules. So, cognate interactions between NK cells and DCs provide a coordinated mechanism that is involved not only in the regulation of innate immunity, but also in the promotion of appropriate downstream adaptive responses for defence against pathogens.