Since publication of the CDC 2016 Guideline, opioid-related mortality in the USA has doubled and a crisis has developed among the 15-20 million Americans with chronic, moderate-to-severe, noncancer pain. Our aim was to develop a comprehensive alternative approach to management of chronic pain. Analytic review of the clinical literature. Published science provides a solid framework for the management of chronic non-cancer pain, detailed here, even as it leaves many knowledge gaps, which we fill with insights from clinical experience. There is a sufficient basis in science and in clinical experience to achieve adequate control of chronic pain in nearly all patients in a way that adequately balances benefits and potential harms.