The benefit of chemotherapy in the treatment of advanced colorectal cancer has now been clearly demonstrated with several studies reporting advantages in terms of overall survival, quality of life and effective palliation following chemotherapy plus supportive care in comparison to supportive care alone. However, the survival benefit achieved with the current 5-fluorouracil (5-FU)-based regimens is modest and thus investigations are ongoing to identify more effective agents with novel mechanisms of action. The three new agents likely to have the greatest impact in the near future are the thymidylate synthase inhibitor ZD1694 (TomudexR), the topoisomerase I inhibitor irinotecan (CamptoR) and the new platinum compound, oxaliplatin (L-OHPR). Promising response rates of 26 and 20% have been reported with ZD1694 in patients with advanced colorectal cancer in phase II and III studies, respectively. In a European phase II study, irinotecan has achieved response rates of 19% in chemotherapy-naive patients and 18% in pretreated patients with advanced disease. Oxaliplatin has mainly been investigated in combination with continuous infusion 5-FU, with response rates of 29-58%. Other agents currently in development include monoclonal antibodies (e.g. 17-1A and MN-14), protein synthesis inhibitors (e.g. RA 700) and angiogenesis inhibitors (e.g. PF 4).