One in 10 Americans experience chronic pain. Although opioids do play a role in the management of pain, long-term opioid use may lead to adverse effects. Endocrine-related adverse effects have been described but remain poorly recognized. Opioid-induced adrenal insufficiency occurs because of suppression of hypothalamic-pituitary-adrenal communication and may be challenging to diagnose but has been reported in 9% to 29% of patients receiving long-term opiate therapy. Little data exist to guide case detection and patient management.