Colorectal cancer is the second leading cause of cancer death in western countries. The prognosis is strongly correlated to the TNM-staging system and patients with stage T3-4 and/or node positive disease are at high risk for locoregional or distant relapse. It is now widely accepted that patients with node positive colon cancer should be offered postoperative adjuvant chemotherapy. Evidence is accumulating that six months' adjuvant fluorouracil plus leucovorin is equivalent to twelve months' fluorouracil and levamisole, which reduces cancer related deaths by more than 30%. Other adjuvant treatment approaches are perioperative regional chemotherapy or monoclonal antibody treatment, and the results of trials comparing these different treatment options alone or in combination are eagerly awaited. In rectal cancer, the risk of locoregional recurrence can be more than 50% and this event is associated with a deterimental effect on quality of life. The technique of mesorectal excision and the use of radiotherapy, alone or in combination with chemotherapy, have evolved as the most important measures for prevention of locoregional recurrence. In addition, chemotherapy has proven to be effective in reducing metastatic relapse and prolonging survival. The timing of radiotherapy (pre- versus postoperative) and the optimal combination of chemotherapy with radiation are presently important research issues in resected rectal cancer. In both colon and rectal cancer, a common theme emerging from the experience of the last few decades is that administration of dose-intensive fluorouracil is key for the success of adjuvant treatment.