Human papillomavirus (HPV) infection can lead to the development of cervical cancer, the second most common cancer-related cause of death in women in the world. The availability of HPV vaccines provides a new and exciting opportunity for cervical cancer prevention. Currently available phase II and III trial data suggest that HPV vaccines are highly effective in preventing infection with HPV-16 and -18, the two types responsible for approximately 70% of cervical cancers worldwide. In order to determine how best to successfully implement a vaccination program, there are a number of factors that need to be considered in addition to vaccine efficacy. These include the choice of a disease endpoint, the duration of vaccine efficacy, the HPV types included in the vaccine, vaccine costs, vaccine coverage, and how the availability of an effective vaccination program may affect screening for those countries that have a successful screening program in place. For settings in which screening is already in place, there will need to be a careful consideration of new approaches to screening, including screening less frequently and using new screening tests or strategies. For settings that have a high burden of cervical cancer but that have not implemented screening, additional trial and registry data that not only confirm the initial results showing high efficacy but also show significant reductions in pre-cancer, and ultimately cancer, will provide reassurance that a decision to implement an HPV vaccination program is sound.