BACKGROUND: The pervasive disease of chronic pain is a common challenge for the clinical rehabilitation professional. Concurrent with physical and emotional symptoms, pain-related cognitive impairment has been reported. Although opioid analgesics are frequently prescribed, concern exists that opioids possess adverse cognitive effects of their own. OBJECTIVES: To review the neuropsychological and neuroanatomical sequelae of chronic non-malignant pain and opioid therapy, to clarify roles and benefits of neuropsychological assessment in a chronic pain population, and to provide recommendations for clinical practice and future research. METHODS: This non-systematic review sought to provide a comprehensive synthesis of relevant neurobiology, neuroimaging, neuropsychological, and rehabilitation research literatures. We included citations from seminal and current texts as well as relevant original and review articles from 1980-2012 in PubMed and PubMedCentral online research databases. DISCUSSION AND SUMMARY/CONCLUSIONS: To date, evidence from opioid studies suggests only mild deficits in specific cognitive domains (e.g., memory, attention/concentration) and only under specific conditions (e.g., dose escalations). Additionally, neuroimaging and neuropsychological evidence suggests that pain itself results in cognitive sequelae. Methodological improvements in future research will allow for better delineation of the contributing effects of pain and opioids, with an overall goal of improving evidence-based clinical treatment recommendations. © 2013 - IOS Press and the authors. All rights reserved.