Experiments in animals and population-based studies have shown the efficacy of nonsteroidal antiinflammatory drugs in colorectal cancer prevention. COX-2 is overexpressed in dysplastic and neoplastic epithelium. COX-2 is a key-enzyme in several tumorigenic pathways, such as promotion of tumor angiogenesis. Non-selective inhibition of COX enzyme demonstrates a protective effect as well, suggesting that more than one mechanism takes place in neoplastic transformation. Blockade of COX enzyme by NSAIDs down-regulates its metabolic product prostaglandin E2. Inhibition of PGE2 seems to have a negative effect in cancer occurrence. Induction of apoptosis is another mechanism that explains the protective effect of NSAIDs. The recently discovered PPARdelta factor, is also overexpressed in neoplastic tissue, and may be a mediator through which COX-2 exerts its oncogenic effect.