Since the late 1970's, increasing evidence from single-arm phase II studies has indicated that combined modality therapy yields a complete response rate of approximately 80-90% in most patients with squamous cell cancers of the anal canal. Surgery, most commonly an abdominoperineal resection, is reserved for salvage therapy. Although patients with large primary tumors (>5 cm) have a lower complete response rate of 50-75%, the majority of patients may be spared a colostomy and have an excellent overall survival. This chapter reviews the recent literature of patients treated for squamous cell, basaloid, and cloacogenic carcinoma (collectively defined as squamous cell cancer) of the anal canal.