Accumulating evidence points to brain reorganization with chronic pain. It seems that the grey matter of the neocortex dynamically changes with chronic pain and this reorganization is pain type specific. In parallel to the anatomical changes, brain functional properties change as well, and the best evidence for condition type functional reorganization is now documented in resting state brain activity, where one can identify a core set of brain networks commonly disturbed with chronic pain, as well as condition specific functional properties. Moreover, brain functional network properties provide a signature for existence and for emergence of chronic pain both in humans as well as in rodent models for pain chronification. It is common clinical knowledge that although a very large patient population presents with similar injuries that give rise to pain, only a small minority of them develop chronic pain. Thus the critical question in the field of pain research is: what characteristics differentiate between those that develop chronic pain and the ones who properly recover from their injury into health. Complimenting the human study there is now evidence in animal models regarding brain reorganization with pain chronification.