Tissue resident memory T cells (T) are enriched in non-lymphoid tissues and represent a formidable barrier against invading pathogens and tumors. T are armed with deployment ready effector molecules which combined with their frontline location allows them to be early organizing centers of our immune defense. Despite their autonomous nature, T rely on careful collaboration with other immune and non-immune cells located within the barrier organ to exert their superior protective role. Here, we highlight recent studies focusing on cellular interactions that regulate T establishment and function. A deeper understanding of these processes is instrumental in designing new means to target T for desirable outcomes in infectious diseases, cancers and autoimmunity.