Gastric cancer remains a leading cause of cancer-related deaths worldwide, although its incidence has been steadily declining during recent decades. Expression of cyclooxygenase-2 (COX-2) is elevated in gastric carcinomas and in their precursor lesions. COX-2 expression associates with reduced survival in gastric cancer patients, and it has also been shown to be an independent factor of poor prognosis. Several molecular mechanisms are involved in the regulation of COX-2 expression in gastric cancer cell lines, including signal transduction pathways activated by Helicobacter pylori. In gastric tumor models in vivo the role of COX-2 seems to be predominantly to facilitate tumor promotion and growth.