With increased prescription of opioids has come increased recognition of adverse consequences, including narcotic bowel syndrome (NBS). Characterized by incompletely controlled abdominal pain despite continued or increasing doses of opioids, NBS is estimated to occur in 4.2-6.4% of patients chronically taking opioids. Patients with NBS have a high degree of comorbid psychiatric illness, catastrophizing and disability; comorbid substance abuse must also be considered among this population. NBS should be distinguished from opioid-induced bowel disorder, which results from the effects of opioids on gastrointestinal motility and secretion. By contrast, the mechanisms of NBS are probably centrally mediated and include glial cell activation, bimodal opioid modulation in the dorsal horn, descending facilitation of pain and the glutaminergic system. Few treatments have been rigorously studied. A trial of opioid detoxification resulted in complete detoxification for the vast majority of patients with reduction in pain symptoms; however, despite improvement in pain, approximately half of patients returned to opioid use within 3 months. Improved strategies are needed to identify patients who will respond to detoxification and remain off opioids. Comorbid psychiatric and substance abuse disorders are barriers to durable response after detoxification and should be actively sought out and treated accordingly. An effective patient-physician relationship is essential.