Genital infection with human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Genital or anal infection with oncogenic types of HPV, particularly types 16 and 18, can cause precancerous lesions of the squamous epithelium. Infection with human immunodeficiency virus (HIV) increases the risk for HPV-associated genital neoplasias in both women and men. Detectable cervical and anal HPV infection is more prevalent among women and men with HIV infection than among those who are HIV-seronegative, and the magnitude of the increase in prevalence is proportionate to the severity of immunosuppression. Coinfection with HIV and HPV increases the risk for genital intraepithelial neoplasia, and the increase in this risk also reflects the severity of immunosuppression. One difficulty complicating elucidation of the association between HIV and HPV infections is that the risk factors for acquisition and transmission of the two viruses are similar. The strength of this association represents a burgeoning health problem, yet there are no treatment guidelines aimed specifically at HIV-infected individuals with HPV-associated genital neoplasias. Treatment of HPV-associated cervical disease in HIV-infected women may be further complicated by a greater risk of treatment failure and recurrence than exists among HIV-seronegative women; it is not known whether dysplasia progresses to invasive disease more rapidly in women infected with HIV. A thorough understanding of the associations among HIV, HPV, and HPV-associated disease is essential to the development of effective strategies for intervention and prevention.