Natural killer (NK) cells and dendritic cells (DCs) are recruited to inflammatory tissues in response to infection. Following priming by pathogen-derived products, their reciprocal interactions result in a potent activating crosstalk that regulates both the quality and the intensity of innate immune responses. Thus, pathogen-primed NK cells, in the presence of cytokines released by DCs, become activated. At this stage they favor DC maturation and also select the most suitable DCs for subsequent migration to lymph nodes and priming of T cells. In addition, a specialized subset of NK cells might directly participate in the process of T-cell priming via the release of interferon (IFN)gamma. Thus, the reciprocal crosstalk between NK cells and DCs that is induced by microbial products not only promotes rapid innate responses against pathogens but also favor the generation of appropriate downstream adaptive responses.