摘要:Background The most essential goal of medicine and public health is to prevent harm ( primum non nocere ). This goal is only fully achieved with primary prevention, which requires us to identify and prevent harms prior to human exposure through research and testing that does not involve human subjects. For that reason, public health policies place considerable reliance on nonhuman toxicological studies. However, toxicology as a field has often not produced efficient and timely evidence for decision making in public health. In response to this, the U.S. National Research Council called for the adoption of evidence-based methods and systematic reviews in regulatory decision making. The U.S. Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the European Food Safety Agency (EFSA) have recently endorsed these methods in their assessments of safety and risk. Objectives In this commentary we summarize challenges and problems in current practices in toxicology as applied to decision making. We compare these practices with the principles and methods utilized in evidence-based medicine and health care, with emphasis on the record of the Cochrane Collaboration. Discussion We propose a stepwise strategy to support the development, validation, and application of evidence-based toxicology (EBT). We discuss current progresses in this field produced by the Office of Health Assessment and Translation (OHAT) of the National Toxicology Program and the Navigation Guide works. We propose that adherence to the Cochrane principles is a fundamental prerequisite for the development and implementation of EBT. Conclusion The adoption of evidence-based principles and methods will enhance the validity, transparency, efficiency, and acceptance of toxicological evidence, with benefits in terms of reducing delays and costs for all stakeholders (researchers, consumers, regulators, and industry). Citation Mandrioli D, Silbergeld EK. 2016. Evidence from toxicology: the most essential science for prevention. Environ Health Perspect 124:6–11; http://dx.doi.org/10.1289/ehp.1509880