To date, very few studies have investigated the role of muscle dysfunction in the pathogenesis of osteoarthritis (OA). Using largely indirect evidence, this article hypothesizes that motor and sensory dysfunction of muscle may be important factors in the pathogenesis of articular damage and are not simply a consequence of joint damage. A new paradigm is constructed to better describe the complex interrelationship between muscle sensorimotor dysfunction, joint damage, and disability in OA. If the hypothesis is correct, because muscle is a relatively plastic tissue, maintaining well-conditioned muscles may delay or prevent the onset of OA, and rehabilitation exercise therapy that reverses muscle sensorimotor dysfunction may ameliorate the effects of OA.