Patients with ulcerative colitis have an increased risk for developing colon cancer compared to the general population. The risk is related to the extension of the disease and its duration. This risk is the same for Crohn's colitis patients of equal extension and duration. By chemoprevention we mean the use of specific natural or synthetic chemical agents to reverse, suppress or prevent progression to invasive cancer. The chemopreventive agents for colon cancer are either of natural origin (vitamins, minerals, food constituents) or synthetic chemicals (difluoromethyl ornithine) and pharmaceutical agents (aspirin, oltipraz). Apart from folate, no other agent has so far been used in vivo for the prevention of colon cancer in long-standing inflammatory bowel disease. The use of folate was, however, not primarily intended to prevent cancer but to enhance folate absorption in ulcerative colitis. From retrospective studies, within the framework of cancer surveillance programmes, it became evident that folate supplementation may play a positive role as a chemopreventive agent against colorectal cancer in patients with long-standing, extensive ulcerative colitis. There is also evidence suggesting that folate supplementation may contribute to regulation of rectal cell proliferation in ulcerative colitis patients. There is a real need for multicentre, randomized, prospective clinical studies in order to evaluate the promising role of folate in preventing colorectal cancer in patients with long-standing inflammatory bowel disease.