Natural killer (NK) cells play important roles in innate defense against infectious agents particularly viruses and also tumors. They mediate their effects through direct cytolysis. release of cytokines and regulation of subsequent adaptive immune responses. NK cells are equipped with sophisticated arrays of inhibitory and activation receptors that regulate their function. In this review we illustrate some of the major evolutionary relationships between NK cell receptors among different animal species and what some of the major mechanisms are that give rise to this diversity in receptor families, including the potential roles of pathogens such as viruses in driving receptor evolution. (C) 2008 Elsevier Ltd. All rights reserved.