AbstractContinued increases in overdose deaths and recent declines in life expectancy call for need to adopt comprehensive public health approaches to the United States opioid crisis and to establish an infrastructure to avert future crises. Successfully addressing the challenges posed by the crisis requires a translational, integrated approach that combines the contribution of neuroscience, pharmacology, epidemiology, treatment services and prevention. It also is critical to integrate interventions across settings, including healthcare, justice, education and social service systems. This review highlights four interconnected themes: (1) social determinants of health and disease; (2) person-centered approaches for prevention and treatment; (3) bridging the gap between implementation science and practice; and (4) using data to build learning systems of care, relevant to public health approaches to address the opioid crisis. We discuss how across these four themes taking into account the influence of developmental factors on brain function and sensitivity to environmental stimuli including drugs, addressing the complex interactions between biological and social factors, and promoting an ongoing dialogue across disciplines and settings will help accelerate public health advances that are evidenced based and sustainable to address the current opioid crisis and avert future ones.