In recent years, significant advances have been achieved in the treatment of colorectal cancer, including the use of adjuvant chemotherapy following surgery in patients with colon cancer and the use of palliative chemotherapy for metastatic disease. Further potential for improvements in outcome for patients with colorectal cancer is provided by the introduction of new agents in combined treatment modalities. Although some of these new agents, such as raltitrexed, oxaliplatin and irinotecan, are active in colorectal cancer, single-agent therapy as first-line treatment has failed to demonstrate a substantial increase in survival. However, preclinical studies have indicated that combination treatments have the potential benefit of enhanced response rates. One such agent, raltitrexed, is currently under investigation in combination with 5-FU (bolus and infusional), oxaliplatin, cisplatin, irinotecan and anthracyclines, principally in patients with advanced colorectal cancer, but also in patients with other tumours. Similarly, combinations of adjuvant or neo-adjuvant radiotherapy and chemotherapy are being investigated and can offer a benefit in the treatment of rectal, oesophageal, pancreatic and gastric cancer. Promise for the future, therefore, appears to lie in combined treatment modalities which are expected to provide superior alternatives to current standard treatments.