It has been estimated that genital human papillomavirus (HPV) is the most common sexually transmitted infection in the US. Nononcogenic types, such as HPV type 6 (HPV-6) and HPV-11, can cause benign or low-grade cervical cell changes, genital warts, and recurrent respiratory papillomatosis. Oncogenic types can cause cervical and other anogenital cancers; oncogenic HPV types are detected in 99% of cervical cancers worldwide. A quadrivalent HPV vaccine to prevent HPV-6, HPV-11, HPV-16, and HPV-18 was licensed for use in the US in June 2006 and an application for Food and Drug Administration licensure was submitted for a bivalent HPV vaccine to prevent HPV-16 and HPV-18 in March 2007. Currently in the US, the quadrivalent HPV vaccine is recommended for routine immunization of girls aged 11 and 12 years, and catch-up immunization is recommended through age 26 years. Monitoring the impact of prophylactic HPV vaccines will be useful for understanding the population level impact of vaccination. In this report, the authors provide a brief review of the epidemiology of HPV infection and an overview of prophylactic HPV vaccines and postvaccine licensure monitoring. Cancer 2008;113:(10 suppl):2995–3008. Published 2008 by the American Cancer Society.