Human papillomavirus (HPV) infection is the most common sexually transmitted infection in the United States. Modeling estimates suggest that more than 80% of sexually active women will have acquired genital HPV by age 50 years. Although most infections are transient and asymptomatic, persistent infection with high-risk types of HPV can lead to precancerous lesions and progress to cancer. In June 2006, the US Food and Drug Administration licensed the first vaccine to prevent cervical cancers and other diseases in women. This quadrivalent vaccine protects against HPV-6, HPV-11, HPV-16, and HPV-18, which are responsible for 70% of cervical cancers and 90% of genital warts. Several studies have been published examining the vaccine's efficacy, duration, immunogenicity, and safety. Questions and controversy remain regarding mandatory vaccination, need for booster doses, and cost-effectiveness.