ABSTRACT: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and a significant cause of anogenital malignancies, precancer lesions, and cutaneous disease. Human immunodeficiency virus (HIV)-positive individuals have a higher prevalence of HPV infection and HPV-associated anogenital disease compared to age-matched HIV-negative controls. Data suggest that there has been little reduction in HPV-associated disease since the introduction of highly active antiretroviral therapy (HAART). The authors believe that cervical and anal cancer screening using Pap tests should be offered to all HIV-positive individuals, but the infrastructure to identify (via colposcopy and high-resolution anoscopy) and treat precancer lesions must be present. Treatment of HPV-associated anogenital disease depends on the size, location, and grade of the lesion, whereas a variety of ablative and excisional therapies are available. Prophylactic and therapeutic HPV vaccines are promising as future interventions for disease control in at-risk populations such as HIV-infected women and men.