Memory T cells (TM) are important components of the immunological memory. Resident memory T cells (TRM) are a subset of TM that reside long-term at sites of previous infection. This thesis investigated the functioning of virus-induced TRM in the brain. Brain TRM (bTRM) proved to be potent and autonomous defenders of the brain against a viral re-infection by rapidly acquiring proliferative and cytotoxic programs as well as by producing cytokines. Thereby, bTRM protected this important and vulnerable organ against otherwise fatal immunopathological disease. In contrast to this beneficial role of bTRM, virus-induced bTRM that recognized a neo-self-antigen presented by CNS-resident cells triggered a local inflammation and an autoimmune-like disease. Accordingly, inflamed brain areas of patients suffering from the human autoimmune disease Multiple Sclerosis contained high numbers of bTRM. This work therefore highlighted a potential double-edged role of bTRM. While virus-specific bTRM are potent immune defenders of the CNS against re-infection, self-reactive bTRM likely contribute to brain autoimmune diseases.