The major goal of clinicians when treating acute musculoskeletal injuries is to return athletes to their pre-injury level of function, ideally in the shortest time possible and without compromising tissue-level healing. In this regard, a commonly used intervention is the taking of NSAIDs. These are used to limit the amount and duration of inflammation, and to control pain. While NSAIDs have become synonymous with the management of acute musculoskeletal injuries, their efficacy has yet to be proven. This is of particular concern in view of recent research investigating the latest class of NSAIDs - selective cyclo-oxygenase-2 inhibitors (COXIBs). COXIBs were developed to reduce the adverse gastrointestinal (GI) effects of traditional NSAIDs. While they have beneficial anti-inflammatory and analgesic properties, and appear to facilitate earlier return to function following acute injury, the effect of COXIBs on tissue-level healing is currently unknown. In experimental animal models of acute injury, COXIBs have been shown to be detrimental to tissue-level repair. Specifically, they have been shown to impair mechanical strength return following acute injury to bone, ligament and tendon. Clinically, this may have implications for ongoing morbidity and future injury susceptibility. However, the current animal studies have limited translation to the clinical setting, particularly because of significant limitations relating to drug use and dosage in these studies. There is currently no randomised, controlled trial evidence of the tissue-level effects of COXIBs on acute musculoskeletal injuries. In addition to questions relating to the effect of COXIBs on tissue-level healing, further questions regarding the use of these agents have been raised given a recent link being shown between one COXIB (rofecoxib) and an increased risk for adverse cardiovascular events. Whether this finding is related to the individual properties of rofecoxib or is a class phenomenon is the subject of ongoing investigation. However, in light of the potential risks associated with using COXIBs, an acceptable and possibly safer alternative in the management of acute musculoskeletal injuries may be to use traditional NSAIDs. Traditional NSAIDs do carry the potential for greater adverse GI effects and their clinical effects on tissue-level healing remain relatively unknown. However, they do not appear to be associated with adverse cardiovascular effects, and they are effective pain relievers and cheaper alternatives.