This review describes how a mismatch between the knowledge produced by scientists and the evidence demanded by regulators has emerged, and how society has struggled to find definitive answers to questions of safety, for an important flame retardant chemical in current use — Deca-BDE. This has involved two key disciplines: analytical chemistry and toxicology. Within the chemistry, a lack of standardized methodologies among scientists has resulted in a persistent yet largely undeclared failure to replicate results within the discipline. Within the toxicology, the quest for innovative, curiosity-driven research by university scientists in preference to using validated standard protocols, designed to promote consistency within the risk assessment process, has prompted questions about the credibility and relevance of scientific findings. Yet scientific laboratories have compelling reasons to do things the way they do in the cause of producing new knowledge, pointing to a sustained gap between the aims and practices of research scientists and those of risk management. A more rigorous scientific process that treats different elements of input data as discrete pieces of evidence is needed to ensure that science rather than politics will always define chemical safety.