Cyclooxygenases are the rate-limiting enzymes in the production of prostaglandins. Cyclooxygenases have long been recognized as important during inflammatory processes, and inhibitors are among the most commonly prescribed and used therapeutic agents in the world. They are commonly used to treat arthritic conditions and are frequently used to manage pain from musculoskeletal conditions, including soft tissue injury, fracture, and after both bone and soft tissue surgeries. Since the discovery of a second isoform of cyclooxygenase (cyclooxygenase-2, or Cox-2), selective agents designed to inhibit a single isoform have been developed. However, the cyclooxygenase enzymes are ubiquitously expressed and are involved in a number of metabolic processes in a variety of tissues. The role of cyclooxygenase in bone repair remains controversial and here we review current knowledge and present additional information suggesting a role for these enzymes in three critical steps in reparative bone formation: chondrogenesis, chondrocyte differentiation, and osteoblast differentiation. A more complete molecular understanding of the events involved in these processes and the role of cyclooxygenases will provide important information that will benefit the care of orthopaedic patients.