The mucosal immune system is constantly exposed to a wide range of commensal and potentially pathogenic microbial species. Chronic exposure to foreign organisms makes generation of an appropriate immune response critical in maintaining a balance between elimination of harmful pathogens, peaceful coexistence with commensals, and prevention of autoimmunity. Intestinal intraepithelial lymphocytes provide a first line of defense at this extensive barrier with the outside world, and as such, understanding their role in immunity is critical.