Nonsteroidal anti-inflammatory drugs (NSAIDs) are a common cause of gastrointestinal ulceration. Chronic NSAID use increases the risk of ulcer bleeding or perforation 3- to 4-fold. NSAID-induced injury results from both local effects and systemic prostaglandin inhibition. New evidence suggests that the systemic effects on prostaglandin production may vary between NSAIDs. The majority of NSAID-induced ulcers are asymptomatic. They may be treated by discontinuing the NSAID and using standard ulcer therapy. Patients taking NSAIDs who are at a high risk for a GI complication should also receive therapy to decrease their risk for ulceration. In this review the epidemiology, pathogenesis, risks, treatment and prophylaxis of NSAID-induced gastrointestinal complications are discussed.