Anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma (ASCC) are on the rise in the United States, especially among men who have sex with men, HIV-positive or other immunocompromised patients, and women with a history of cervical, vaginal, or vulvar cancer. Strong evidence supports the human papillomavirus as the causative factor in anal dysplasia; reducing the risk of HPV infection can reduce rates of ASCC. High-risk patients should be screened for AIN, but no universal screening guidelines exist, and more studies are needed to develop a national protocol for screening and management of patients with AIN.