Anal cancer accounts for only 4% of all cancers of the lower alimentary tract. However, the incidence is rising – possibly due to the higher incidence of persons engaging in anal-receptive intercourse. Chemoradiotherapy has become the standard treatment for localized anal squamous cell cancer (except for very small tumors of the anal margin). Improvement in therapeutic techniques such as intensity-modulated radiation therapy reduces toxicity, improves compliance, and therefore translates into better oncologic outcomes. Patients who fail the initial chemoradiotherapy should be considered for abdominoperineal resection or palliative chemotherapy. Patients with metastatic anal cancer are treated with cisplatin-based chemotherapy with or without radiotherapy (or surgery) to control the primary tumor. Cetuximab-based treatment may be used in patients with metastatic anal cancer (KRAS wild type) after failure of cisplatin-based chemotherapy.