The US Food and Drug Administration issued draft guidance designed to facilitate development of non-opioid therapies for chronic pain. The recommendations outline clinical trial design considerations for drugs aimed at reducing opioid use or preventing initiation. The FDA is open to expedited regulatory pathways, although challenges remain due to the subjective nature of pain and difficulty in identifying surrogate endpoints. The guidance aims to spur innovation amid the opioid epidemic, encouraging safer, alternative analgesic options.