This Review perspective analyzes the parallel ‘opioid crises’ – one of access, the other of excess – affecting different demographic groups in distinct regions of the world, in terms of a knowledge gap between the founding 20th-century regulatory frameworks around ‘drugs’, including opioids, and evolving 21st-century clinical developments in public health, palliative care, addiction medicine, and regulatory sciences. Identifying the parallel crises as such is a positive step that can enable governance and science to catch up to one another and realign. As it is now, the opioid crises are acting as brakes on development as defined by the United Nations (UN) 2030 Agenda for Sustainable Development (SDGs). Both crises affect UN member states’ ability to reach the Goal 3 ‘Ensure healthy lives and promote well-being for all at all ages’ of the Sustainable Development Goals (SDGs). Among the nine targets for Goal 3, the two opioid crises affect progress toward Target 3.5, on strengthening the prevention and treatment of substance abuse, including narcotic drug abuse, and Target 3.8, providing Universal Health Coverage (UHC), and adequate access to essential medicines. The parallel opioid crises, which both represent misalignment between anachronistic governance structures and epistemic developments, have several things in common beyond the opioid molecules themselves: regulatory and health system deficits that interact pathologically with baked in cultural stigma around psychoactive substances, stigma evident in the designation of these substances in international law as ‘narcotic drugs’. Community regeneration, educational development, and governance reforms can now replace politicized rather than evidence-based and public health–promoting drug policies that block progress toward both SDG 3 targets in different countries for different reasons. Quantification of serious health-related suffering (SHS) pertaining to a range of health conditions and demographic groups now provides the epidemiological evidence to legitimate such a timely paradigm shift.