5-FU is the best available single drug in advanced colorectal disease. After systemic administration approximately 15% of the patients achieve a short-lived objective remission. Survival is not prolonged by therapy. Several chemotherapy combinations have in preliminary phase II studies given higher response rates (30-50%), but when evaluated in controlled studies, no advantage over single-drug 5-FU has been verified. At present, two combinations, MOF-S and sequential MTX/5-FU/Leucovorin seem promising, but more experience is needed before general acceptance. In cases of liver dissemination, regional hepatic infusion therapy causes objective tumour regression more often than systemic therapy. However, median survival is most likely the same for both treatment modalities, and since hepatic artery infusion is the most expensive therapeutic modality, routine use of hepatic artery infusion is discouraged. Outside clinical trials, systemic or regional chemotherapy is hardly indicated in advanced colorectal disease apart from certain selected symptomatic patients.