Evidence-based medicine (EBM) and evidence-based decision-making (EBDM) were intended to revolutionize health care and health policy. Thus far they have not. A great deal of research has demonstrated the persistent ubiquity of error in health care, wide and unjustifiable variations in practice and the minimal impact of decision aids such as clinical practice guidelines. This paper attempts to explain why EBM and EBDM have remained largely unrealized ambitions. It advances 10 propositions that together constitute a general theory of indifference to research-based evidence. Some of these propositions are conceptual (e.g. the epistemic resistance to the randomized trial), some are empirical (e.g. the impact of the corruption of science by industry), some are cognitive (e.g. human problems are holistic while science is typically fragmented and narrative free) and some are normative (e.g. the primary goal is not adherence to methods, but to make better decisions with better outcomes, irrespective of their origins). EBM and EBDM over-reached, and their failure was, as a consequence, inevitable. However, with corrective action on a number of fronts, research-based evidence can and should be more influential. The first step is to reconceive EBM and EBDM as habits of mind rather than a toolbox and to recognize that the sociology of knowledge is as important as its technical content.