Currently licensed influenza vaccines rely predominantly on the induction of strain-matched hemagglutination inhibition antibody responses. These vaccines have a proven record of safety and efficacy in preventing influenza-induced illness and complications. However, they do not confer protection to all vaccinated individuals, and the protection they afford is short-lived, particularly in older adults. Hemagglutination inhibition titers induced by these vaccines are considered correlates of protection, but recent data demonstrate that this is not always the case. It is clear that better insight is needed into the immune responses that correlate with protection against human influenza. Influenza vaccines that can induce cross-reactive cellular immune responses (CD4(+) and/or CD8(+) T-cell responses) might correct some of the shortcomings of currently used influenza vaccines. In the future, the use of infection-permissive and disease-modifying vaccines that allow for the induction of cross-reactive T-cell responses may become a valuable complement to the administration of trivalent inactivated influenza vaccines.