Initial treatment for rectal cancer offered little cure and high morbidity by removing the entire rectum by means of either an abdominal or perineal approach. In 1908 Miles described the combined abdominoperineal resection (APR) technique. Later, Dixon performed a partial proctectomy for proximal tumors via a low-anterior resection (LAR). As the relationship between lymphatic removal and improved disease-free and overall survival became clear, the total mesorectal excision (TME) became the cornerstone of rectal cancer surgery. These techniques ensure tumor-free proximal, distal and radial margins and achieve the goals of an oncologically sound anatomic resection. Due to technological advances and improved understanding of tumor biology, sphincter-sparing approaches, such as an extended LAR, local excision and TEM, have increasingly been used to maintain functional defecation and improve patients’ quality of life. In 1990, the National Institutes of Health (NIH) recommended adjuvant chemotherapy for stage II and III rectal cancers and more recent trials have demonstrated decreased local recurrence and increased 5-year survival rates in patients receiving neoadjuvant radiation or chemoradiation (chemo-XRT) therapies. Current curative treatment for rectal cancer involves complex multidisciplinary planning combining oncologically sound surgical principles with sphincter saving techniques, neoadjuvant and adjuvant radiation and chemotherapy. The vast majority of anal canal and anal margin cancers are squamous cell in origin and as such, this chapter will focus on this entity. Unless specifically mentioned, all references of anal canal or anal margin cancer refer to squamous cell cancer.