Most patients who undergo surgery recover uneventfully and resume their normal daily activities within weeks. Nevertheless, chronic postsurgical pain develops in an alarming proportion of patients. The prevailing approach of focusing on established chronic pain implicitly assumes that information generated during the acute injury phase is not important to the subsequent development of chronic pain. However, a rarely appreciated fact is that every chronic pain was once acute. Here, we argue that a focus on the transition from acute to chronic pain may reveal important cues that will help us to predict who will go on to develop chronic pain and who will not. Unlike other injuries, surgery presents a unique set of circumstances in which the precise timing of the physical insult and ensuing pain are known in advance. This provides an opportunity, before surgery, to identify the risk factors and protective factors that predict the course of recovery. In this paper, the epidemiology of chronic postsurgical pain is reviewed. The surgical, psychosocial, socio-environmental and patient-related factors that appear to confer a greater risk of developing chronic postsurgical pain are described. The genetics of chronic postsurgical pain are discussed with emphasis on known polymorphisms in human genes associated with chronic pain, genetic studies of rodent models of pain involving surgical approaches, the importance of developing accurate human chronic postsurgical pain phenotypes and the expected gains for chronic postsurgical pain medicine in the post-genomic era. Evidence is then reviewed for a preventive multimodal analgesic approach to surgery. While there is some evidence that chronic postsurgical pain can be minimized or prevented by an analgesic approach involving aggressive perioperative multimodal treatment, other studies fail to show this benefit. The transition of acute postoperative pain to chronic postsurgical pain is a complex and poorly understood developmental process, involving biological, psychological and social-environmental factors.