Manual therapy (MT-) is moving beyond its empirical origins and into an era of evidence-based practice. Mechanisms for the appearance of clinically observed symptoms and signs are beng incorporated into its clinical reasoning process. The recent, but well-documented phenomenon, central sensitization, is recognized as being one such mechanism. Anatomical, physiological, behavioural and clinical evidence demonstrate that, in addition to input from the periphery, central sensitization can be enhanced or maintained by supraspinal processes involving cognitions, attention ('focussing') and emotions. These forebrain products may, therefore, make a significant contribution to the symptoms and signs of common musculoskeletal presentations such as 'non-specific' back pain and fibromyalgia. The evidence can also be interpreted to provide MT with an acceptable role in the management of these patients.