In contrast to systemic viral infections such as lymphocytic choriomeningitis virus (LCMV), infection of the skin with herpes simplex virus-1 (HSV-1) or Vaccinia virus (VacV) activates naïve antigen-specific CD8+ T cells that subsequently traffic into and differentiate into TRM almost exclusively at the site of infection [17–19], suggesting that local inflammation, at least in part, is critical for promoting the acquisition of the TRM phenotype. The gene discussed is CD8A; the disease is infection.