Non steroidal anti-inflammatory drugs (NSAIDs) have diverse clinical applications through modulation of oxidative processes and cell signalling. Observations that these agents may inhibit human colorectal carcinogenesis have produced great excitement. However, comparative data relating to their chemopreventative effectiveness or to relevant mechanisms of action remains unclear. This review considers the clinical and epidemiological evidence for colorectal tumour prevention by NSAIDs against current concepts of drug mechanisms. We also propose areas of further research for potential therapeutic advancement.