The current inactivated influenza virus vaccines induce antibodies that protect against closely related virus strains. They do not, however, protect against antibody-escape variants of seasonal influenza A viruses or new pandemic influenza A viruses emerging from non-human reservoirs. Might boosting influenza A virus-specific CD8+ T cell memory diminish the danger posed by these variant viruses? Pre-existing CD8+ T cell-mediated immunity directed at peptides from conserved internal proteins of the influenza A virus does not prevent infection, but it can promote early virus clearance and decrease morbidity in mice. In this issue of the JCI, Lee et al. show that people who have not been exposed to avian influenza A (H5N1) viruses have cross-reactive CD8+ T cell memory to a wide range of H5N1 peptides (see the related article beginning on page 3478). These peptides could be used to add a CD8+ T cell component to current antibody-focused vaccine strategies with a view to reducing the impact of infection with novel influenza A viruses.