Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs worldwide. They are prescribed for orthopaedic conditions such as osteoarthritis, soft-tissue injuries and fractures. The new generation of NSAIDs, selective cyclooxygenase-2 (COX-2) inhibitors, exhibit analgesic and anti-inflammatory effects equivalent or superior to conventional NSAIDs, while reducing the prevalence of adverse gastrointestinal events. Several reports from animal and in vitro studies have demonstrated impaired bone healing in the presence of conventional NSAIDs, as measured by a variety of different parameters. More recently, initial studies investigating the effects of selective COX-2 inhibitors on bone healing have yielded similar results, while other reports showed minor or no impairment of the healing process. The purpose of the present review article is the thorough review and analysis of the past 50-year literature and the attempt to get some conclusions about the effect of NSAIDs and selective COX-2 inhibitors on fracture healing and the clinical significance of their use in the management of postoperative and post-fracture pain.