Healthcare providers face the challenging task of managing patients who suffer from chronic nociplastic pain conditions. Pain is a multidimensional experience, and the current approach to managing people in chronic pain often fails to meet the needs of these patients. Novel ways of treating people who suffer from chronic nociplastic pain with classic psychedelic agents may offer a new lens through which to approach their pain. Lysergic acid diethylamide (LSD) and psilocybin are both serotonergic agents with a long history of use in treating people with chronic pain and mental health disorders. The new wave of research into psychedelics for major depressive disorder provides an opportunity to investigate and understand the potential for incorporating these drugs into chronic pain management pathways. This narrative review presents healthcare workers with a framework to understand the method of action of these drugs in chronic nociplastic pain pathways and a brief history into their use. We conducted an online search using Pubmed with keywords ‘chronic pain’ AND/OR ‘psilocybin’ AND/OR ‘lysergic acid diethylamide’ AND/OR ‘psychedelics’ with no date limit applied. We identified further articles that contained information on the neuroscience of psychedelics and the serotonergic system using Google Scholar. During the final stages of writing the article, the latest publications on psychedelics and chronic pain in leading pain journals were again included to update the information.