Studies conducted in HIV-seropositive individuals have enhanced our understanding of the natural history of anal intraepithelial neoplasia (AIN) and of factors predictive of progression to high-grade AIN, the immediate precursor to anal cancer. AIN is frequently detected in HIV-seropositive individuals. Factors that increase the risk for AIN include HIV infection, low current or nadir blood CD4+ cell counts, receptive anal intercourse, oncogenic human papillomavirus (HPV) infection, persistent anal HPV infection, multiple HPV type infections and high anal HPV viral load. This review confirms the importance of high-grade AIN in HIV-seropositive individuals and HIV-seronegative men having sex with men.