The lifetime risk of human papillomavirus (HPV) infection exceeds 50%. HPV infection causes >550,000 cases of cervical and anogenital cancer worldwide annually. Infection also causes precancerous lesions and genital warts. HPV types 16 and 18 cause approximately 70% of HPV-related cancers, and HPV types 6 and 11 cause approximately 90% of cases of genital warts. A quadrivalent vaccine for HPV types 6, 11, 16, and 18 (HPV 6/11/16/18) has been developed for prevention of cervical cancer, genital warts, and vulvar and vaginal precancerous lesions. Prophylactic vaccination of young women was 96%-100% effective in preventing HPV 6/11/16/18-related cervical and anogenital precancers and genital warts. Efficacy remained high for at least 5 years following vaccination. Postvaccination anti-HPV levels in adolescents were superior to those observed in women (the population in which efficacy was shown). Vaccination was generally well tolerated. The vaccine is licensed in >80 countries. It has been added to national vaccination programs, including that of the United States. Widespread use of HPV 6/11/16/18 vaccine is expected to greatly reduce the incidence of HPV-related cancers, precancers, and genital warts.