Objective: TO review the pharmacology, efficacy, safety, tolerability, and pharmacoeconomics of Cervarix and Gardasil, 2 human papillomavirus (HPV) vaccines. Data Sources: English-language articles were obtained by MEDLINE search (1966–February 2006) using the key words human papillomavirus vaccine, Cervarix, and Gardasil. Bibliographies of selected articles were used to identify additional sources. Study Selection and Data Extraction: All available published articles or abstracts reporting the results of human studies of HPV vaccines were reviewed for inclusion in this article. Additional information about ongoing clinical trials was obtained from manufacturers' Web sites. Data Synthesis: Cervarix and Gardasil are recombinant vaccines against HPV. Cervarix targets HPV-16 and -18, which are responsible for 70% of cervical cancers. Gardasil also targets HPV-16 and -18, plus the HPV-6 and -11 types responsible for more than 80% of genital warts. Both vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions, while Gardasil has also been effective in preventing vulvar and vaginal neoplasia and genital warts. Both vaccines have been well tolerated, with the most common adverse effects occurring at the injection site. Phase III trials are ongoing to further evaluate vaccine efficacy. Conclusions: Cervarix and Gardasil are effective for prevention of HPV infection and cervical lesions. Issues remaining to be addressed include duration of protection, efficacy for prevention of cervical cancer, optimal age for vaccination, feasibility of application to the developing world, the ideal combination of HPV subtypes, and the most efficient combination of vaccination and cervical cancer screening.