Use of long-term opioid analgesia has increased significantly in the past decade and dependency on prescribed opioids has been described as a public health emergency in the United States. Opioid analgesia may be associated with excess mortality when compared to other classes of analgesia used in chronic pain. Opioids exert a range of effects across the hypothalamic-pituitary axes, which are potentially dependent on the chronicity of exposure. The largest body of evidence relates to effects upon reproductive hormones, which are mediated through inhibition of hypothalamic GnRH release and, consequently, LH and sex steroids. Hypogonadism may be present in up to 75% of male and 21% of female chronic pain patients treated with opioids. Whilst opioids can alter prolactin, thyrotropin and growth hormone secretion, it is much less clear whether this results in any clinically meaningful sequelae. Several case reports have identified opioids as a cause of secondary adrenal insufficiency. Recently, a small cross-sectional study of opioid-treated chronic pain patients identified adrenal insufficiency in 10% of patients receiving high dose opioids. However, chronic pain is also associated with perturbations in the HPA axis and further work is required to elucidate the effects (and potential mechanisms) of opioids on glucocorticoid production.