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In this farewell lecture, Jonathan Samet—outgoing director of the USC Institute for Global Health—addressed the changing paradigm of evidenced-based decision-making. Science advances knowledge, chiseling at areas of ignorance and reducing uncertainties, which may slow evidence-based decision-making. With regard to environmental pollution, for example, great progress has been made as research has documented the damage done to human and ecosystem system health by man’s activities, motivating action and guiding interventions. However, over recent decades, the paradigm of evidence-based decision-making has been increasingly threatened as powerful stakeholders, with seemingly threatened interests, have undermined scientific evidence by creating doubt and even offering personal and collective beliefs as an equivalent basis for decision-making. The strategy of doubt creation can be traced to actions of the tobacco industry initiated as the evidence mounted showing that smoking causes cancer and other diseases; the same tactics have spread, particularly around environmental pollutants. More challenging is the emergence of outright dismissal of evidence and its replacement by belief, whether consistent with or counter to what is known.