The anal carcinoma is substantially a rare neoplasm. Its incidence, however, also due to HPV infection is increased in the past 30 years. For many years, the surgical treatment has been the first therapeutic option, but with a major impact on quality of life (permanent colostomy) and unclear results on the local control. Radiochemotherapy with 5-fluorouracil (5-FU), mitomycin C, and/or cisplatin is currently the standard of conservative therapeutic approach. Current data show that toxicity, particularly myelosuppression and neurotoxicity, is significantly more frequent in the patients treated with the combined therapy compared with patients treated with antineoplastic drugs alone. The introduction of HAART into clinical practice has had a dramatic impact on the natural history of HIV-related disease, including cancer. Chemotherapy plus HAART-treated patients have a better survival than chemotherapy alone, suggesting that the reduction of opportunistic infections (OIs) morbidity by HAART other than the good performance status of these patients, may improve the overall outcome of the combined treatment patients. Also, the new techniques of intensity modulated radiotherapy (IMRT) seem to have an important role on the lower incidence of side effects and improve local control of the disease.