Epidemiological and experimental studies indicate an inverse relationship between the risk of colon cancer development and intake of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). All NSAIDs are known inhibitors of cyclo-oxygenase, the enzyme responsible for converting arachidonic acid to prostaglandins. Prostaglandins have been implicated in the pathogenesis of colon cancer and it has been suggested that the preventive effect of NSAIDs is due to inhibition of cyclo-oxygenase activity. Cyclo-oxygenase exists in two different isoforms, cyclo-oxygenase-1 and cyclo-oxygenase-2, and data obtained during the last few years have suggested that cyclo-oxygenase-2 might be involved in both human and experimental colon carcinogenesis. The purpose of this review is to provide an update on recent studies regarding cyclo-oxygenase, in particular cyclo-oxygenase-2, in relation to colon cancer in humans and in experimental models.