The extent of cortical neuroplastic changes has been shown to be a key neurophysiological feature that correlates with the level of functional recovery. Therefore, rehabilitation efforts that attempt to maximize cortical reorganization provide the greatest potential for rehabilitation success. This paper reviews the evidence of cortical neuroplastic changes that have been shown to occur in association with experimental or chronic pain disorders. Further, the promising role of novel motor-skill training is discussed in order to best direct the clinician to optimize rehabilitation strategies for patients with musculoskeletal pain disorders.