Opioids are an established option in the analgesic armamentarium for managing moderate-to-severe chronic pain. Long-term opioid use, however, is associated with several potential adverse effects and toxicities, such as peripheral edema, immune suppression, hyperalgesia, sleep apnea, and changes in endocrine function, many of which are not fully appreciated. Opioid endocrinopathy can greatly affect patients, causing reduced sexual function, decreased libido, infertility, mood disorders, osteoporosis, and osteopenia. Furthermore, although opioid endocrinopathy appears to be common, many patients do not report their symptoms, thus causing this adverse effect to go unnoticed and without clinical monitoring, particularly in patients chronically taking the equivalent of ≥ 100 mg of morphine daily. Indeed, diagnosing hypogonadism as opioid-related can be challenged by other influences on endocrine function, such as pain pathophysiology, comorbidities, other drug therapies, and patient age. Management options for opioid endocrinopathy include discontinuing opioid therapy, reducing the opioid dose, switching to a different opioid, and hormone supplementation.