The benefit of exercise for pain control likely comes from the impact of exercise on the endogenous opioid system and on central pain modulatory systems. Patients with some chronic pain conditions seem to have a dysfunctional endogenous pain modulatory system, which should be considered when prescribing exercise. The prescription of exercise for chronic pain must address the biomechanical issues and the psychosocial factors that contribute to the patient’s pain and disability. Patient education, coordination of care within the health care team, and selecting an exercise regimen that is meaningful to and achievable by the patient are all important components to promote a successful rehabilitation program.