Chronic post-operative pain is a major source of suffering and disability. Better standardisation for assessing and reporting chronic post-operative pain is needed. Peripheral and central nervous plasticity seem to play a major role in the development of chronic post-injury pain. Complex mechanisms, including several receptor systems and messenger systems are involved. Thus, it is unlikely that one single agent will solve the problem. Opioids have proven effect both in animal models, experimental human models, and in some clinical models. Timing and dose seem to be of importance. However, it is likely that polypharmacy and multi-modal treatment is necessary to further improve the preventive strategy.