Tissue resident memory CD8 T cells can provide protective immunity against difficult to target pathogens such as Plasmodium and influenza virus, which remain major health burdens. Thus, the generation and manipulation of Trm populations could be a valuable strategy in the development of effective and long-lasting vaccination strategies against these pathogens. However, much remains to be elucidated regarding the mechanisms that govern Trm function, persistence, and ultimately protective capacity. By investigating the basic biology of Trms we aim to improve our understanding of these populations, and ultimately increase our ability to manipulate them in clinical settings.