The impact of the immune system on the etiopathogenesis of neurodegenerative diseases, including Alzheimer's disease, is a rapidly growing area of investigation. Evidence from human patients and animal models implicates neurotropic viral infections, and specifically the antiviral immune response of brain-infiltrating CD8 T cells, as potential drivers of disease pathology. While infiltration and retention of CD8 T cells within the brain following viral infection is associated with improved survival, CD8 T cells also contribute to neuronal death and gliosis which underlie cognitive impairment in several disease models. Here we review the role of antiviral CD8 T cells as potential mediators of cognitive impairment and highlight the mechanisms by which brain-resident CD8 T cells may contribute to neurodegenerative disease pathology.