Natural killer (NK) cells are important mediators of the immune response against microbial pathogens and tumors. There is growing evidence from mouse and human studies that, NK cells exhibit immunoregulatory functions and can limit T cell immunity. NK cell regulatory activity has been demonstrated in a variety of disease models including chronic viral infection, autoimmunity, and transplantation. Depending on the nature of the immune challenge, NK cells use different strategies to limit T cell function, including via cytokines, interactions with NK receptors NKG2D and NKp46, or by perforin-mediated T cell death. Future work should address whether specific subsets of NK cells inhibit T cell responses, and how NK cells acquire immunosuppressive functions.