Vaccines for preventing human papillomavirus (HPV) infection are far along in clinical development and testing, and hold great promise for reducing HPV infections and HPV-associated disease. HPV is the most common sexually transmitted infection in the United States, affecting an estimated 75% of the U.S. population. HPV infection is highly prevalent in sexually active adolescents and young adults. Sexual activity is the most important risk factor for infection, with 64% to 82% of sexually active adolescent girls testing positive for HPV. Clinical manifestations of HPV infection include genital warts, cervical intraepithelial neoplasia (CIN), and invasive cervical cancer, all of which cause significant morbidity and, in the case of cervical cancer, mortality. The majority of HPV-associated disease is caused by 4 HPV types: HPV 6 and 11 are responsible for low-grade genital lesions and more than 90% of genital warts, and HPV 16 and 18 both account for approximately 70% of all high-grade CIN or dysplasia and invasive cervical cancer. Although current screening methods have proven effective in reducing cervical cancer incidence and associated mortality, more than 10,000 women are diagnosed annually and 4000 U.S. women die from the disease each year.