Eicosanoids are arachidonic acid derivatives that include prostaglandins, thromboxanes, and leukotrienes. During the last three decades, it has become evident that these bioactive lipids play a pivotal role in gastric physiology. The goal of the present review is to describe their involvement in the normal regulation of gastric secretion and gastric motility, as well as in gastric mucosal defense. Their role in gastric mucosal mitogenesis, apoptosis, inflammation, and immune modulatory responses is also discussed.