Osteoarthritis (OA) continues to be a debilitating disease worldwide, to date, no therapies have been definitely proven to modify disease progression or moderate symptom relief long term other than joint replacement. A contributing factor may be the lack of attention to the potential role of the periarticular enthesis and development and progression of OA. The enthesis is the site of attachment for a tendon, ligament, or joint capsule to the bony skeleton, thereby allowing centralized transmission and dissipation of mechanical loads. Because of this design, the enthesis is a site of stress concentration subject to inflammation during sports-related activities or spondyloarthropathies, which may lead to long-term degeneration. Our hypothesis is that functional incompetence of the enthesis resulting from either degenerative or inflammatory changes could be an initiating factor for OA and may thus provide a novel basis for the development of future disease management in this phenotype of patients.