Tissue resident memory T cells and viral immunity

•Tissue resident memory T cells (TRM) are the main surveyors of non-lymphoid tissues.•TRM activate innate and adaptive immunity and establish an antiviral state within tissues.•TRM provide protection against numerous viral pathogens in multiple tissues.•Vaccines aimed at promoting TRM hold promise for the future. Tissue resident memory T cells (TRM) constitute a recently identified T cell lineage that is responsible for frontline defense against viral infections. In contrast to central and effector memory T cells, which constitutively recirculate between tissues and blood, TRM reside permanently within tissues. As the main surveyors of non-lymphoid tissues, TRM are positioned to rapidly respond upon reinfection at barrier sites. During a viral reinfection, TRM trigger the local tissue environment to activate and recruit immune cells and establish an antiviral state. Consistent with this function, there is empirical evidence that TRM accelerate control in the event of reinfection or possible reactivation of latent infections in solid organs and barrier tissues. Here we review recent literature highlighting the protective functions of TRM in multiple viral challenge models and contextualize the implications of these findings for vaccine development.