Although postoperative pain remains incompletely controlled in some settings, increased understanding of its mechanisms and the development of several therapeutic approaches have substantially improved pain control in past years. Advances in our understanding of the process of nociception have led to insight into gene-based pain therapy, the development of acute opioid-induced hyperalgesia, and persistent postsurgical pain. Use of specific analgesic techniques such as regional analgesia could improve patient outcomes. We also examine the development of new analgesic agents and treatment modalities and regimens for acute postoperative pain.