Cyclooxygenase-2 (COX-2) is an enzyme induced by inflammatory and mitogenic stimuli and results in enhanced synthesis of PGs in inflamed and neoplastic tissues. It is associated with cell proliferation and growth, in various cancerous conditions. We review the potential mechanisms of cancer reduction with COX-2 inhibitors and the preclinical evidence suggesting their effectiveness. Results of our study show that COX-2 is a regulatory factor for a number of pathways that can result in cancer. COX-2 makes cells resistant to apoptosis and promote angiogenesis, metastasis and cancer cell cycle by controlling number of targets. We found that, COX-2 selective inhibitors (like celecoxib and NS-398) can suppress the cancer both by COX-2 dependent and COX-2 independent pathways. COX-2 inhibitors can also produce synergic effects when used with other anti-cancer therapies. Thus, it is concluded that COX-2 selective inhibitors may be promising agents for prevention and treatment of cancer.