NK cells show cytotoxicity and cytokine production upon recognition of virus-infected cells and play an important role in conferring protective immunity against virus infection. Patients who lack functional NK cells are susceptible to severe infectious diseases such as herpesvirus infection. In addition, when NK cells are removed from cytomegalovirus-resistant mice, the virus titre after infection is markedly increased and the mice are likely to die due to infection. However, the exact mechanism of how NK cells recognise virus-infected cells has remained unclear for a long time. Recent findings of the presence of virus-specific NK cell receptors and their ligands on virus-infected cells have provided a new vision of a protective role of NK cells in virus infection. Furthermore, the recognition of virus-infected cells by paired receptors consisting of activating and inhibitory receptors was found to correlate with the degree of host susceptibility to virus infection. Current topics on the role of NK cells in anti-virus immunity are reviewed. Copyright © 2004 John Wiley & Sons, Ltd.