Chronic inflammation is a known risk factor for gastrointestinal cancer. The evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) suppress the incidence, growth, and metastasis of gastrointestinal cancer supports the concept that an NSAID target, cyclooxygenase (COX) and its downstream bioactive lipid products, may provide one of the links between inflammation and cancer. Preclinical studies have demonstrated that the COX-2-PGE2 pathway can promote gastrointestinal cancer development. Although the role of this pathway in cancer has been extensively investigated for two decades, only recent studies emerge describing its effects on host defenses against transformed epithelial cells.