A number of factors have recently coalesced to bring hormone testing and treatment to the field of pain care. Uncontrolled, severe pain as well as opioid drugs have a profound impact on the endocrine system. Because pain is a potent stressor, it initially causes pituitary, adrenal, and gonadal hormones to elevate in the serum. If severe pain goes uncontrolled for too long, however, hormone levels deplete in the serum. The finding of abnormal (too high or low) serum hormone levels serve as biomarker of endocrinopathies, which helps inform the clinician that enhanced analgesia as well as hormone replacement may be necessary. Adequate, physiologic levels of some specific hormones are necessary for optimal analgesia, neuroprotection, and neurogenesis. Although not a substitute for opioids, some hormone replacements may minimize their use. We know that the central nervous system produces a group of hormones called neurohormones whose natural function is neuroprotection and neurogenesis. Their clinical use in centralized pain states is new, and early reports indicate that they may have considerable benefit for treatment.