Mariapia A. Degli‐Esposti

Summary Natural killer (NK) cells are the prototype innate effector lymphocyte population that plays an important role in controlling viral infections and tumors. Studies demonstrating that NK cells form long‐lived memory populations, akin to those generated by adaptive immune cells, prompted a revaluation of the potential functions of NK cells. Recent data demonstrating that NK cells are recruited from the circulation into tissues where they form long‐lived memory‐like populations further emphasize that NK cells have properties that mirror those of adaptive immune cells. NK cells that localize in non‐lymphoid tissues are heterogeneous, and there is a growing appreciation that immune responses occurring within tissues are subject to tissue‐specific regulation. Here we discuss both the immune effector and immunoregulatory functions of NK cells, with a particular emphasis on the role of NK cells within non‐lymphoid tissues and how the tissue microenvironment shapes NK cell‐dependent outcomes.