Postoperative incisional pain is a unique and common form of acute pain. Although ample evidence indicates that an efficeous postoperative pain treatment reduces patient morbidity and patient outcome, recent studies demonstrate that about 50-70% of patients experience moderate to severe pain after surgery indicating that postoperative pain remains poorly treated. Perhaps important reasons for this quandary are distinct mechanisms of incisional nociception compared to other pain conditions limiting our regimen to drugs designed for other clinical pain problems. Another reason might be the lack of an in depth knowledge about the pathophysiology and neuropharmacology of postoperative pain. Basic research offers important insights in the mechanisms of postsurgical incisional pain and the translation of experimental results into clinical practice will have important implications on the improvement of new multimodal treatment regimens based postoperative pain mechanisms. In the present review, recent developments in experimental postsurgical incisional pain research will be described and their possible relevance for clinical practice discussed.