Although techniques for acute pain management have improved in recent years, a dramatic reduction in the incidence and severity of chronic pain following surgery has not occurred. Amputation and thoracotomy, although technically different, share the commonalities of unavoidable nerve injury and the frequent presence of persistent postsurgical neuropathic pain. The authors review the risk factors for the development of chronic pain following these surgeries and the current evidence that supports analgesic interventions. The inconclusive results from many preemptive analgesic studies may require us to reconceptualize the perioperative treatment period as a time of gradual neurologic remodeling.