Tough but constructive criticisms of evidence-based medicine (EBM) have without doubt informed the evolution and serial reconstitutions of this approach to clinical decision making and behaviour. Yet, concerns about EBM persist and as EBM changes in response to reflection and criticism, so too do the criticisms themselves. This paper describes our current understanding of EBM and, to identify opportunities for the continuing evolution of EBM, discusses some key attributes of EBM that still or now cause us concern. Specifically, these attributes are the nature of evidence in EBM; the unknown effectiveness of EBM; the clinician-centric focus of EBM; and the potential of EBM to harm patients.