NSAID gastropathy is characterized by subepithelial hemorrhages, erosions, and ulcers. Approximately half of patients taking NSAIDs regularly have gastric erosions and 10% to 30% have gastric ulcers. Although gastric lesions are common at endoscopy, clinically significant problems are uncommon. There is no correlation between NSAID gastropathy and upper abdominal symptoms frequently experienced by patients taking NSAIDs. Subepithelial hemorrhages and erosions may cause minor bleeding, but ulcers must be present for major bleeding, gastric outlet obstruction, or perforation to occur. NSAID use is associated with an increased risk of gastrointestinal complications; this risk is increased with older age, a history of peptic ulcer, a history of gastrointestinal bleeding, higher doses of NSAIDs, and concomitant use of corticosteroids. Perhaps three-quarters of 1% of patients taking NSAIDs for 6 months develop clinically significant complications ascribed to ulcers or erosions. NSAIDs do not cause a diffuse histologic gastritis (i.e., inflammatory cell infiltration). Any such gastritis is owing to H. pylori infection and appears to be unchanged by NSAID ingestion. Although some authors have suggested that NSAIDs cause a diffuse chemical or reactive gastritis, this has not been clearly documented in studies involving pre- and post-treatment biopsies. Cotherapy with misoprostol decreases the incidence of endoscopically visualized gastric and duodenal ulcers and appears to decrease the incidence of ulcer complications. In the future, development of NSAIDs that do not cause damage to the gut (e.g., COX-2-selective NSAIDs and NO-NSAIDs) may prevent any concerns about NSAID gastropathy and NSAID-associated gastrointestinal complications.