Complex regional pain syndrome (CRPS) is clinically characterized by pain, abnormal regulation of blood flow and sweating, edema of skin and subcutaneous tissues, trophic changes of skin, appendages of skin and subcutaneous tissues, and active and passive movement disorders. It is classified into type I (previously reflex sympathetic dystrophy) and type II (previously causalgia). Based on multiple evidence from clinical observations, experimentation on humans, and experimentation on animals, the hypothesis has been put forward that CRPS is primarily a disease of the central nervous system. CRPS patients exhibit changes which occur in somatosensory systems processing noxious, tactile and thermal information, in sympathetic systems innervating skin (blood vessels, sweat glands), and in the somatomotor system. This indicates that the central representations of these systems are changed and data show that CRPS, in particular type I, is a systemic disease involving these neuronal systems. This way of looking at CRPS shifts the attention away from interpreting the syndrome conceptually in a narrow manner and to reduce it to one system or to one mechanism only, e.g., to sympathetic-afferent coupling. It will further our understanding why CRPS type I may develop after a trivial trauma, after a trauma being remote from the affected extremity exhibiting CRPS, and possibly after immobilization of an extremity. It will explain why, in CRPS patients with sympathetically maintained pain, a few temporary blocks of the sympathetic innervation of the affected extremity sometimes lead to long-lasting (even permanent) pain relief and to resolution of the other changes observed in CRPS. This changed view will bring about a diagnostic reclassification and redefinition of CRPS and will have bearings on the therapeutic approaches. Finally it will shift the focus of research efforts.