Since 1958 there has been intense efforts in adjuvant systemic therapy for colorectal cancer. Peri-operative chemotherapy with HN2, TSPA + FUDR produced no clear-cut prolongation of disease-free survival. Short-term (two courses) and long-term (18 months) therapy with 5-FU by the Veterans Administration surgical Adjuvant Group is reported to give marginal increases (7--9%) in survival at 5 years. These findings are confirmed by the COG study of prolonged 5-FU which shows prolongation of disease-free survival of borderline statistical significance for Dukes' C colon (P = 0.051) + rectum (P = 0.016). Short-term benefit to 18 months was conferred by prolonged 5-FU in the VASAG + COG studies, for patients who have had a palliative resection. Combination chemotherapy might be more active, but no results are available from the controlled trials utilizing 5-FU + MeCCNU or immunotherapy. Preoperative irradiation in the VASAG studies resulted in downstaging in terms of operative findings of lymph node involvement and was of survival benefit in those patients have an AP resection for cure or palliation of rectal cancer (P less than 0.02). More intensive preoperative radiation programs are ongoing, as well as postoperative radiation with and without chemotherapy. Further progress awaits the discovery of truly active chemotherapy programs, as well as better techniques of radiation enhancement.