Significant advances have been made in the treatment of anal cancer. Anal sphincter function can be preserved in most patients by using chemoradiation therapy as definitive treatment. Close clinical follow-up is imperative for supportive care and assessment of response. Salvage surgery should not be pursued unless clinical evidence of disease progression is shown. Routine biopsies are discouraged, because positive findings on biopsy after chemoradiation therapy in the absence of clinical evidence of disease progression are not predictive of persistent disease.A dose-response relationship has been observed for radiation and chemotherapy. However, treatment-related toxic effects can be significant, and toxic effects that mandate interruptions in treatment can compromise local control. Aggressive supportive care and clinical strategies that further reduce treatment-related toxic effects are necessary for further therapeutic advances. Strategies to minimize toxic effects and improve rates of local control are being investigated. They include the development of therapeutic approaches that are specific for tumor stage and that optimize the effectiveness of chemoradiation therapy.