NK cells are innate lymphocytes that play a key role in the control of various viral infections. Recent studies indicate that NK cells may acquire some features of adaptive immune cells, including the formation of long-lived memory cells. A large and growing body of data indicates that NK cells regulate the adaptive immune response as well. The function and the activation status of NK cells are tightly regulated by signals induced by a broad range of inhibitory and activating cell surface receptors and cytokines released by other immune cells. Here, we review the function of mouse NK-cell receptors involved in virus control and in the regulation of the adaptive immune response. In addition, we discuss viral strategies used to evade NK-cell-mediated control during infection. Finally, the role of several activating Ly49 receptors specific for mouse cytomegalovirus (MCMV), as well as some controversial issues in the field, will be discussed.