Despite exciting progress in the understanding of advanced gastro-intestinal cancer, the prognosis of these diseases is still poor because of limited treatment options. Curative surgery is often not possible or worthwhile due to tumour spread. Systemic chemotherapy typically shows low response rates of short duration, and a potential palliative benefit is limited by systemic toxicity. This problem could be circumvented by local chemotherapy administration, and this review will summarize the actual role of regional intra-arterial chemotherapy in the treatment of advanced gastro-intestinal cancer. Due to its beneficial effect on survival and quality of life, hepatic artery infusion chemotherapy is a viable option for the treatment of non-resectable metastases confined to the liver from colorectal cancer. Regional chemotherapy for locally or regionally advanced or recurrent cancer of stomach, pancreas, or rectum must still be regarded as an experimental treatment with sometimes impressive pain relief. When systemic chemotherapy and radiotherapy have failed in non-resectable (recurrent) rectal cancer, regional chemotherapy via internal iliac arteries may provide satisfactory palliation. The response rates of intra-arterial chemotherapy in gastro-intestinal cancer are better than, or at least as good as, those of all other palliative treatment modalities. In terms of survival, besides one controlled trial showing better survival after liver infusion, the role of regional chemotherapy needs to be further evaluated.