Available data from small heterogeneous studies suggest that 9% to 29% of patients receiving long-term treatment with opiates have development of adrenal insufficiency. However, predictors and the timing of the OIAI onset are unclear. Given the widespread use of narcotics in every field of medicine, physicians should be aware of the potential for endocrine-related adverse effects, in particular OIAI. We suggest careful consideration of OIAI in any patient receiving long-term opiate therapy who manifests symptoms and signs suggestive of adrenal insufficiency. Prospective large studies need to be designed with the goals of elucidating factors associated with OIAI, developing the best approach to case detection of OIAI, and establishing an appropriate management and monitoring plan.