Central pain mechanisms are deeply embodied in the psychophysical problem of pain. They are located in the brain and spinal cord and are becoming increasingly recognised as playing a major role in the generation and maintenance of pain and disability associated with neuromusculoskeletal problems. Central mechanisms participate in all pain states, acute and chronic. They are universally influenced by psychological and physical factors, whether or not a specific pathology can be identified. Misconceptions are that manual therapy operates on peripheral mechanisms without influencing the central ones and that when a central problem exists, psychological management is preferable. In reality, as key players in the healing process, central mechanisms are profoundly affected by manual therapy even when it is directed at a peripheral problem. Treatment of peripheral mechanisms can be performed through central techniques because both peripheral and central mechanisms are always part of the same clinical problem. Consequently, manual therapy must change its mindset from a peripheral standpoint and integrate central mechanisms into clinical practice as a means of improving therapeutic efficacy and to prevent the descent of acute pain into chronic.