Chemoprevention is the use of natural or synthetic compounds in order to reverse. suppress or prevent the carcinogenic process. Among the many pathways dysregulated during the carcinogenic process, cyclooxygenase-2 (Cox2) seems to be one of the most promising pathways to target in order to achieve chemopreventive and anticancer effects. Indeed, Cox2 overexpression contributes to the carcinogenic by at least 5 different mechanisms including transformation of procarcinogens on carcinogens, pro-inflammatory and immunomodulatory effect, resistance to apoptosis, angiogenesis and invasion progression... This review will focus on the rationale and the ongoing research areas related to chemopreventive approaches targeting Cox2.