Under the influence of cytokines associated with innate immunity, natural killer (NK) cells rapidly become activated and migrate to sites of infection. Upon contact with infected parenchyma they proliferate, release cytokines and/ or kill cells harboring pathogens. Multiple stimulatory and inhibitory receptors can provide the integrated signals that trigger this contact-mediated NK-cell function. Recent work has begun to define the ligands for these receptors in the context of infection by certain well-studied viruses. These results, in addition to future work involving other pathogens, will provide an understanding of the molecules present on parasitized cells that mark them as targets of innate immunity.