Nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant cause of gastric mucosal injury and bleeding, particularly in elderly patients. The mechanism of this injury appears to be, at least in part, a disruption of normal cytoprotective mechanisms by the inhibition of prostaglandin production. Acute injury results from the local effect of some drugs and may resolve with time. Chronic injury may occur with any NSAID and may often be asymptomatic until a complication occurs. Treatment of either lesion centers around NSAID withdrawal and standard ulcer therapy. Although routine prophylaxis of all patients is not indicated, those patients with a history of NSAID injury or other risk factors may need preventive measures if they are treated with NSAIDs. Oral prostaglandins, such as misoprostol, are effective in the prevention of NSAID-induced injury. The efficacy of sucralfate and H2-blockers in this setting appears promising but requires further study.