Clinical studies on adjuvant chemotherapy in colorectal cancer started 30 years ago, but some proof of its effectiveness did not come until recently. Only randomized prospective studies can provide definite evidence in this regard. Obviously, the potential value of an effective adjuvant treatment for a frequent disease such as colorectal cancer is enormous. Randomized studies had failed to provide evidence in favour of adjuvant chemotherapy in colon cancer until a recently reported study on 5-fluorouracil and levamisole. As of today, the latter regimen may be considered as the reference one for adjuvant chemotherapy in Dukes C colon cancer. In rectal cancer some studies displayed statistically significant results in favour of adjuvant chemotherapy: however, sufficient data are still unavailable to support adjuvant chemotherapy as standard treatment. On the contrary, postoperative radiotherapy is definitely effective in decreasing local relapses. Studies are underway on the combination of chemotherapy and radiotherapy in rectal cancer. In addition to systemic chemotherapy, portal infusion of cytotoxic drugs has been tested in colorectal cancer. Controlled studies are underway, but available results would not seem to support regional treatment. Recent improvement in the chemotherapy of advanced colorectal cancer has probably occurred through the pharmacologic modulation of 5-fluorouracil by leucovorin. If this will be confirmed, one will be able to resort to more effective multidrug regimens than those tested so far and an improvement in adjuvant chemotherapy may be anticipated too.