© 2015 Future Medicine Ltd. NK cells constitute a population of lymphocytes involved in innate immune functions. They play a critical role in antiviral immune surveillance. Viruses have evolved with their host species for millions of years, each exerting a selective pressure upon the other. As a corollary, the pathways used by the immune system that are critical to control viral infection can be revealed by defining the role of viral gene products that are nonessential for virus replication. We relate here the battery of resources available to NK cells to recognize and eliminate viruses and reciprocally the immune evasion mechanisms developed by viruses to prevent NK cell activation.