The use of nonsteroidal antiinflammatory medications (NSAIDs) and nutraceuticals, such as glucosamine and chondroitin, is common among athletes at all ages and levels of participation. The use of these drugs has significant effects on pain and swelling associated with injury; however, this use does have significant risks to the gastrointestinal, hepatic, and renal organ systems. In the athlete with degenerative changes in the joints, the use of these medications can become chronic and lead to an increased risk of adverse effects. The purpose of this article is to examine the incidence of injury in sports, the prevalence of osteoarthritis in athletes, and the use of common over-the-counter medications and supplements. In addition, the mechanism of action, adverse side effects, and behavioral patterns for use of these medications will be analyzed.