We have focused on cyclooxygenase, the key enzyme in prostaglandin synthesis, from our basic knowledge regarding the enzyme, to its clinical application in the field of oncology. We will present evidence that this enzyme is intimately associated with carcinogenesis, invasion, metastasis, and the response of tumors to current therapeutic modalities in a variety of human malignancies. We will also discuss the applications of cyclooxygenase inhibitors tochemoprevention and to the sensitization of tumors to conventional anti-cancer therapies.