Human papillomavirus (HPV) is a significant health care burden in the United States. The majority of sexually active men and women will be infected with HPV at some point in their lives and are subject to developing human papillomavirus-associated disease. Current estimates suggest that 20 million Americans are currently infected, and more than 5 million new infections occur each year. The prevalence of human papillomavirus is highest in populations in their late teens and early twenties, with nearly half of all new human papillomavirus infections occurring within 3 years of first intercourse. HPV is the necessary cause of genital warts, cervical intraepithelial neoplasia, and invasive cervical cancer. As such, human papillomavirus is responsible for significant medical morbidity and health care costs. Screening with cervical cytology has significantly reduced mortality rates; however, approximately 3900 women will die in 2005 from cervical cancer in the United States. Human papillomavirus DNA testing has shown promise in identifying high-grade abnormalities as an adjunct to traditional cytology, and should be used according to guidelines established by the American Cancer Society and the American College of Obstetricians and Gynecologists. The epidemiology of HPV infection and a brief introduction to the natural history of HPV infection will be presented here.