The clinical utility of nonsteroidal anti-inflammatory drugs (NSAlDs) to manage pain and inflammation is limited by adverse side effects. Although effective analgesic and anti-inflammatory agents, NSAlDs are associated with side effects that are a consequence of nonspecific inhibition of both cyclooxygenase-1 (COX-1) and 1 cyclooxygenase-2 (COX-2).The primary adverse events associated with NSAID therapy are upper gastrointestinal (GI) ulceration, perforation, or bleeding, all of which involve mucosal damage of varying severity and can be asymptomatic and I occur with little warning. Clinicians who prescribe NSAIDs should be able to identify patients who are at risk of an NSAID-induced GI adverse event and to detect and manage the event should one occur. The use of COX-2-specific inhibitors to manage pain and inflammation may minimize the risks of NSAID-associated toxicities.