It is now well accepted that inadequately treated pain and associated stress response have significant physiologic and psychologic consequences, which may lead to organ dysfunction and increase postoperative mortality and morbidity. In addition, unrelieved postoperative pain reduces the ability to participate in rehabilitation programs, leading to poor postoperative outcomes. Furthermore, poorly controlled pain can potentially increase the incidence of chronic persistent postoperative pain. Thus, pain delays recovery and discharge home and reduces quality of life and patient satisfaction. Overall, inadequately treated pain increases resource use and health care costs. Therefore, an improvement in perioperative analgesia is not only desirable for humanitarian reasons but is also essential for the potential reduction in postoperative morbidity, improved health-related quality of life, and reduced health care costs. Chronic persistent postoperative pain is common but often under-recognized or misdiagnosed. The first step in preventing persistent postoperative pain is to accept that it can occur after surgery. Despite numerous reports of persistent postoperative pain resulting in distress and disability, it has been ignored. The prevalence of chronic persistent postoperative pain appears to vary with the type of surgery as well as the surgical approach. Therefore, the use of a surgical approach that minimizes tissue trauma is crucial. However, it is not clear why some patients develop persistent pain, whereas others undergoing the same surgical procedure do not. Other risk factors include pre-existing pain, the extent of acute pain, and certain personality factors (psychologic vulnerability). It appears that the intensity of acute postoperative pain (particularly movement-evoked pain) is an important predictor of persistent postoperative pain. Therefore, it is necessary to provide effective and rational early interventions, which reduce postoperative pain not only at rest but also on movement. Multimodal analgesia techniques, including regional analgesia (epidural analgesia or continuous peripheral nerve blocks), COX-2 inhibitors (NSAIDs and COX-2 specific inhibitors), and opioids have been recommended for providing dynamic pain relief with a lower incidence of side effects. In addition, NMDA antagonists (eg, ketamine), a2 agonists (eg, clonidine and dexmedetomidine), and anticonvulsants (eg, gabapentin and pregabalin) have been investigated. However, the use of these adjunct analgesics remains controversial and needs to be evaluated in larger studies. It is imperative that future acute pain studies collect appropriate data, including preoperative pain intensity and physiologic and psychologic risk factors. In addition, data regarding the location and length of surgical incisions and handling of nerves and muscles should also be obtained. Furthermore, postoperative follow-up, including quantitative and descriptive pain assessment, patient function, and physical signs and symptoms as well as postoperative interventions (eg, radiation therapy and chemotherapy), should be collected for at least 1 year. Areas of interest include identifying high-risk individuals, because focused interventions may be beneficial for these patient populations. In addition, the determination and adoption of surgical techniques that will minimize the incidence of chronic postoperative pain are imperative. It is necessary to assess the relationship between the intensity and time course of postoperative pain and the occurrence of persistent postoperative pain. Finally, prospective randomized, controlled studies are needed to determine how different pain management strategies influence the incidence of persistent postoperative pain.