Immune responses are generally divided into innate and adaptive responses, and the efficacy of one is thought to be independent of the other. The regulation of immune responses, however, is complex, and accumulating evidence indicates that multiple interactions between immune effector cells are common and are crucial for the initiation, as well as the outcome, of these responses. Dendritic cells, long recognized as key initiators of primary adaptive immunity, are now also seen as crucial regulators of aspects of innate immunity, in particular natural-killer-cell function. Reciprocally, natural killer cells can influence the activity of dendritic cells. Here, we review recent exciting progress in this field, and we highlight the impact of this cellular crosstalk on the design of immune-based therapies for control of infection and cancer.