The treatment of rectal cancer has gradually evolved based on our knowledge of the failure patterns. Although results with surgery alone are good in patients with disease limited to the bowel wall and with no lymph node spread, surgery alone is less effective for more advanced disease. Treatment strategies that combine pelvic radiation therapy and 5-fluorouracil-based chemotherapy regimens have significantly improved local recurrence rates and overall survival results for patients with disease extending through the bowel wall or those with positive lymph nodes. Recent studies suggest that methyl CCNU can be dropped from chemotherapy regimens without loss of efficacy. Newer strategies being investigated include modulations of 5-fluorouracil with agents such as leucovorin and levamisole, possibly in combination, and continuous infusions of 5-fluorouracil.