Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely used drugs in the United States. Ulcers are found with an endoscopy in 15%-30% of patients who are using NSAIDs regularly, and the annual incidence of upper gastrointestinal (GI) clinical events is 2.5%-4.5% among those who use NSAIDs regularly. Upper GI symptoms, such as dyspepsia, also occur in up to 60% of patients taking NSAIDs. H2-receptor antagonists when used at standard doses are not effective at preventing gastric ulcers resulting from the use of NSAIDs. Misoprostol effectively decreases NSAID-induced ulcers and GI complications, but issues of compliance (multiple daily doses) and side effects (eg, diarrhea and dyspepsia) may limit its use. Once-daily therapy with proton pump inhibitors has been documented to significantly decrease the development of NSAID-associated ulcers in endoscopic studies, reduce the rate of NSAID-related ulcer complications, and reduce upper GI symptoms in NSAID users.