Vaccines are the only proven effective method for prevention of human infectious diseases. Almost all traditional vaccines require activating immunological memory B cells to secrete neutralizing antibodies against invading pathogens. The complication with influenza viruses is the high viral mutation rate that results in immune escape through modification of the B cell epitopes. Studies of T cell immunity to influenza infection provide an alternative vaccine strategy based on highly conserved T cell epitopes. In this review, we discuss the importance of T cell-mediated immunity in influenza infection and the need for a targeted vaccine approach focused on highly conserved T cell epitopes to mitigate immune escape. We propose 15 highly conserved pan-influenza sequences as potential T cell epitopes-based vaccine targets for broad protection and lasting immunity against variant influenza strains.