A safe, effective and accessible preventive vaccine is our best long-term hope for the control of the HIV/AIDS pandemic. Once the first generation of HIV vaccines are developed, many questions remain unanswered regarding their administration. For instance, which vaccines should be given to whom at what age and how many doses? We argue that pre- and early-adolescents will be one of the main target groups for future HIV vaccines, that is, before the age of exposure to the virus. Historically, immunization has mainly focused on infants. Indeed, vaccines have only occasionally been systematically targeted at adolescents, even in industrialized countries. Delivering vaccines to pre-adolescents and adolescents in developing countries would, to a great extent, be a new challenge. But it is not just HIV/AIDS vaccines that are coming down the pipeline. Herpes simplex type2 (HSV-2) and human papillomavirus (HPV) vaccines are also among the exciting candidate vaccines that may be the agents of change needed to encourage even the poorest countries to develop strategies for reaching adolescents with vaccines and other health services in the coming decade. Together, they may also provide the impetus for changing the paradigm for how vaccines are administered. Not only will more antigens be included in national immunization schedules, but the age of target groups will range much more widely than at present, encompassing older children, adolescents and young adults. While presenting major difficulties for delivery, these new ingredients also offer stimulating opportunities to completely rethink how vaccines are presented, administered and delivered. We predict that even the poorest countries will be looking to developing integrated, sustainable strategies for reaching pre-adolescents and adolescents with vaccines in the coming decade.