There is substantial experimental, clinical and epidemiological evidence that regular use of non-steroid anti-inflammatory drugs (NSAIDs), particularly aspirin, is associated with a reduced risk of colorectal cancer. The protective effect is thought to arise from inhibition of prostaglandin synthesis, although the precise mechanism remains unclear. Of the epidemiological studies carried out, all but one have found that regular use of NSAIDs reduces the risk of colorectal cancer by 30-50%. The consistency of this finding across studies and the magnitude of the reduced risk tend to support a causal association between NSAID use and reduced risk of colorectal cancer. Further, the protective effect increases with longer duration of use, and persists after controlling for other colorectal cancer risk factors. However, these observational studies are limited by inherent biases, potential confounding with other lifestyle factors, and sparse information on dose and duration of use. Only one randomized controlled trial has been carried out, and no reduction in risk was associated with intake of one aspirin per day, though this may be due to the short follow-up period and the low dose of aspirin taken. Further observational studies and randomized controlled trials are needed to confirm the association, to quantify the dosage required for a protective effect, and to identify those patients most likely to benefit.