Background: Use of opioids in the management of pain and its consequences in children presents a substantial challenge. A significant concern in pediatric pain management is the longterm neuropsychological consequences of opioids. Objectives: The authors aim to provide a descriptive review of the current literature surrounding the neuropsychological impact of opioid use in children, along with possible extrapolations from their use in adults and animal models. Study Design: Systematic review of published literature. Setting: Various universities in the United States. Methods: The electronic review for papers published between January 1992 and December 2012 was conducted using Medline/Pubmed, PsychInfo, CINAHL, the Cochrane Library database, and Google Scholar. Results: Findings assessing pediatric pain patients treated with opioids demonstrated no significant differences in intelligence, behavior, vocabulary, or motor skills. One study reported a decrease in a visuo-constructional ability, which measured higher order executive function. Studies from prenatal illicit opioid exposure found poorer performance on measures of language, verbal ability, mathematics, reading, impulse control, and school readiness skills. The literature from adult prescribed opioid users has mixed results. Some showed impairment in the neuropsychological domains of memory, decision-making, attention, concentration, information processing, psychomotor speed, visual special skills, and hand-eye coordination, while others found no differences or revealed improved perceptual-cognitive status, possibly due to the removal of pain as a stressor. Limitations: Very few studies looked into the long term neuropsychological and cognitive effects of the opioids in pediatric population. In an attempt to extrapolate from other groups, this review also included literature from adult patients, prenatal opioid exposure, and animal studies. Conclusion: Opioid medications have the potential to produce long-lasting neuropsychological side effects. However, given the negative consequences of untreated pain, the potential benefit may offset their risk. More studies are needed to clarify this complex interaction.