Complex regional pain syndrome (CRPS) is still a puzzling disease. Although pathophysiologic understanding has improved, not every aspect of this challenging neuropathic pain syndrome has been explored. Typical symptoms of CRPS are sensory, motor, and autonomic dysfunctions. In most cases, CRPS occurs after a fracture, limb trauma, or lesion of the peripheral or central nervous system. Sometimes, symptoms develop without any trauma. Recent pathophysiologic concepts basically consider three major mechanisms: enhanced peripheral neurogenic inflammation, dysfunction of the sympathetic nervous system, and structural reorganization in the central nervous system. Moreover, a genetic predisposition may explain increased vulnerability. Treatment usually requires a multidisciplinary approach, including medical and nonmedical therapies. The common therapeutic aim is to maintain or restore normal function of the affected extremity. Beyond highlighting pathophysiologic concepts, this article describes recent therapeutic approaches.