Dendritic cells (DCs) play a central role in initiating immune responses. Despite this, there is little understanding how different DC subsets contribute to immunity to different pathogens. CD8α+ DC have been shown to prime immunity to HSV. Whether this very limited capacity of a single DC subset priming CTL immunity is restricted to HSV infection or is a more general property of anti-viral immunity was examined. Here, we show that the CD8α+ DCs are the principal DC subset that initiates CTL immunity to sc infection by influenza virus, HSV, and vaccinia virus. This same subset also dominated immunity after iv infection with all three viruses, suggesting a similar involvement in other routes of infection. These data highlight the general role played by CD8α+ DCs in CTL priming to viral infection and raises the possibility that this DC subset is specialized for viral immunity.