Epidemiological studies have shown that the use of nonsteroid anti‐inflammatory drugs (NSAIDs) is associated with reduced risk of gastric cancer. The best‐known target of NSAIDs is the cyclooxygenase (Cox) enzyme. Two Cox genes have been cloned, of which Cox‐2 has been connected with gastric carcinogenesis. Expression of Cox‐2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis. This suggests that Cox‐2–derived prostanoids promote aggressive behavior of adenocarcinomas of the stomach. Cox‐2 expression is especially prominent in intestinal‐type gastric carcinoma and it is already present in dysplastic precursor lesions of this disease, which suggests that Cox‐2 contributes to gastric carcinogenesis already at the preinvasive stage. Our most recent data show that Cox‐2 is expressed in gastric adenomas of trefoil factor 1 deficient mice. Treatment of these mice with a Cox‐2 selective inhibitor, celecoxib, reduced the size of the adenomas. Taken together these data support efforts to initiate clinical studies to investigate the effect of Cox‐2 inhibitors as chemotherapeutic agents and as adjuvant treatment modalities against gastric neoplasias.