Chronic postoperative pain is known to be a significant clinical and economic problem. The estimated mean incidence is high and varies between 10 and 50%, with variations mostly related to procedure-specific conditions. High-risk types of surgeries are e.g. thoracotomy, breast or inguinal hernia surgery and amputations. Although there is increasing knowledge about the incidence of chronic postoperative pain after certain types of surgical procedures, there are only limited data related to the mechanisms and pathophysiology leading to chronic pain after surgery. Neuropathic pain components have been discussed, especially following operations with a high incidence of nerve damage (for example axillary lymphadenectomy). Besides surgical factors it seems that there are a number of other factors which likely increase the risk of chronic postoperative pain. These predictors for the development of chronic postoperative pain are multiple and include individual genetic factors, age and sex of the individual patient, preoperative chronic pain, psychosocial factors, neurophysiological factors, intraoperative nerve and muscle damage, postoperative complications and acute pain in the early postoperative period. Quantitative sensory testing including tests of inhibitory circuits like DNIC might help to predict the risk of individual patients even before surgery has started. The perioperative identification of patients who are at high risk for developing chronic pain after surgery is therefore a major goal for the future. This may help to develop preventive treatment strategies and avoid treatments with side effects for patients who are not at risk for developing chronic pain after surgery. Due to a lack of appropriate data for sufficient preventive approaches an effective postoperative acute pain management and a nerve-conserving surgical technique are the major keys in the prophylaxis of chronic postoperative pain.