Addiction to opioid analgesics is an important and yet underinvestigated clinical issue, which has substantial implications in opioid therapy for chronic pain management. Problematic opioid use, including compulsive opioid seeking and addiction, arises in some fraction of opioid-treated chronic pain patients. The connection between chronic pain and opioid addiction is a complex interplay between psychological, epidemiological, and neurobiological factors. Herein, we explore this critical relationship.