For locally advanced squamous cell carcinoma of the anal canal, efforts to discover effective treatments that would protect sphincter preservation led to the development of combined chemoradiotherapy, which, when administered appropriately, is curative. While the standard of combined modality chemoradiotherapy has minimally changed over the past 30 years, various chemotherapeutic and biologic agents, as well as novel methods for delivering radiation, have enhanced the treatment of anal carcinoma and are continuously being explored. This review examines the risk factors associated with anal carcinoma, and subsequently discusses the current standard of care from diagnosis through surveillance, paying attention to the pivotal trials that have shaped modern treatment paradigms.