NK cells express a limited number of germline-encoded receptors that identify infected or transformed cells, eliciting cytotoxicity, effector cytokine production, and in some circumstances clonal proliferation and memory. To maximize the functional diversity of NK cells, the array and expression level of surface receptors vary between individual NK cell "clones" in mice and humans. Cytomegalovirus infection in both species can expand a population of NK cells expressing receptors critical to the clearance of infected cells and generate a long-lived memory pool capable of targeting future infection with greater efficacy. Here, we discuss the pathways and factors that regulate the generation and maintenance of effector and memory NK cells and propose how this understanding may be harnessed therapeutically.