Anal cancer comprises malignancies of the anal canal principally of two morphologic variants: squamous cell carcinoma (SCC) and adenocarcinoma. In most settings, SCC compromises more than 70% of cases. In the general population, anal cancer is uncommon, with age-standardised incidence rates mostly between 1 and 2 per 100000 per year. However, incidence of anal SCC is increasing by 1-3% per year in developed country settings. High-risk human papillomavirus (HPV) types can be detected in 80-90% of all anal SCC cases, making it second only to cervical cancer in the closeness of its association with this virus. HPV-16 can be detected in ~90% of HPV-positive cases of anal SCC. Case-control studies have demonstrated that sexual risk factors (homosexuality in men and multiple sexual partners in women) are strongly associated with anal cancer risk. Other risk factors include immune deficiency and tobacco exposure. Anal cancer rates are highest in homosexual men, particularly in those who are HIV-positive, in whom anal cancer is among the most common of all cancers. Vaccination against HPV holds great promise for anal cancer prevention for those not already HPV-infected. For the current generation of adult high-risk populations, screening programs to allow early detection and treatment are under investigation.