Early data from randomized controlled trials consistently show that prophylactic human papillomavirus virus-like particle (HPV VLP) vaccines are effective in preventing infection and lesions caused by the targeted HPV type(s). Two vaccines, a bivalent HPV-16/18 VLP vaccine and a quadrivalent HPV-6/11/16/18 VLP vaccine, are currently undergoing evaluation in phase III trials with anticipation of receiving regulatory approval for use in immunization programs worldwide. Both vaccines have the potential to substantially reduce HPV-related morbidity and mortality. This review focuses on published data from clinical trials of these two vaccines.