Most currently available vaccines target acute infectious agents such as polio, smallpox and influenza virus. The development of vaccines to persistent infectious agents has proven much more difficult. Although it is possible to generate T cell responses to such viruses, these responses are currently unable to prevent the establishment of infection, and immune control may be lost during the chronic phase. Recent advances have increased our understanding of the interactions between persistent viruses and the available T cell repertoire, and will guide approaches to the generation and maintenance of an 'ideal' T cell response.