Human papillomavirus (HPV) infection causes cervical cancer, a significant portion of anal, genital, and oropharyngeal cancers, genital warts, and recurrent respiratory papillomatosis. In June 2006, a quadrivalent HPV-6/11/16/18 vaccine (Gardasil/Silgard) was licensed in the United States, and subsequently in the European Union (September 2006). It has since been approved in 121 countries, with >74 million doses distributed globally as of March 2011. As the incidence of HPV infection peaks 5-10 years after the onset of sexual activity, preadolescents and adolescents represent an appropriate target group to implement HPV vaccination programs so as to achieve the maximal public health benefit. In this article, we provide an overview of the prophylactic efficacy of the vaccine in young women who were found to be negative to at least one of the four vaccine HPV types, thus approximating sexually naive adolescents. Because adolescents are also at high risk for other infections which are preventable by currently available vaccines, the development of concurrent immunization strategies may lead to better compliance, thereby contributing to the overall goal of protection against preventable diseases. We also summarize concomitant administration studies with meningococcal, diphtheria, tetanus, and pertussis vaccines, which were conducted in adolescents aged 9-15 years. Prophylactic efficacy in other populations (males aged 16-26 years) is also summarized along with long-term safety and efficacy studies.