Colorectal cancer is one of the leading causes of death in western countries. The prognosis is strongly correlated to the TNM-staging system and patients with stage T3-4 and/or N positive disease have a high risk for local or distant relapse. It is now widely accepted that patients with stage III disease should be offered postoperative adjuvant chemotherapy with 5-fluorouracil (5-FU) and levamisole by which cancer related death is reduced by 32%. The use of 5-FU plus folinic acid is based on the experience gathered in metastatic disease where its superiority over 5-FU alone has been proven in randomized trials. In the adjuvant setting, however, this regimen has only been studied in comparison to untreated controls of combined stage II and stage III patients. Due to different patient selection criteria, data are currently not directly comparable to standard 5-FU/levamisole and the results of the intergroup trial 0089 have to mature. Regional short term adjuvant treatment (7 days) seems to be as effective as long term systemic therapy (12 months). Knowledge has been accumulated within at least 8 randomized trials and the NSABP-CO2 trial, with more than 1000 patients, is now demonstrating improved survival with regional therapy applied shortly after curative resection. The EORTC has just started to randomize patients to receive systemic vs. regional therapy or both modalities and will hopefully clarify the role of either strategy. Immunotherapy with autologous tumor cell-BCG or monoclonal antibody treatment also improves patients survival and is currently investigated in randomized comparison to standard 5-FU/levamisole.(ABSTRACT TRUNCATED AT 250 WORDS)