Selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat a variety of musculoskeletal conditions. The efficacy of these medications has been proved, although the risks have not been clearly delineated. Nonselective NSAIDs are associated with gastrointestinal, renal, and hematologic complications. The risks of using selective NSAIDs may include cardiovascular adverse events. The most appropriate agent should be chosen by considering the possible complications as well as the patient's risk profile.