Despite existing international, regional and national guidance on how to obtain valid consent to health-related research, valid consent remains both a practical and normative challenge. This challenge persists despite additional evidence-based guidance obtained through conceptual and empirical research in specific localities on the same subject. The purpose of this paper is to provide an account for why, despite this guidance, this challenge still persist and suggest conceptual resources that can help make sense of this problem and eventually mitigate it’. This (...) paper argues that despite the existence of detailed official guidance and prior conceptual and empirical research on how to obtain valid consent, the question of ‘how to obtain and ascertain valid consent to participation in health-related research’ cannot always be fully answered by exclusive reference to pre-determined criteria/guidance provided by the guidelines and prior research’. To make intelligible why this is so and how this challenge could be allayed, the paper proposes six concepts. The first five of these are intended to account for the persistent seeming inadequacies of existing guidelines. These are fact-skepticism; guideline insufficiency; generality; context-neutrality and presumptiveness. As an outcome of these five, the paper analyzes and recommends a sixth, called bioethical reflexivity. Bioethical reflexivity is reckoned as a handy tool, skill, and attitude by which, in addition to guidance from context-specific research, the persisting challenges can be further eased. Existing ethical guidelines on how to obtain valid consent to health-related research are what they ought to be – general, presumptive and context-neutral. This explains their seeming inadequacies whenever they are being applied in concrete situations. Hence, the challenges being encountered while obtaining valid consent can be significantly eased if we appreciate the guidelines’ nature and what this means for their implementation. There is also a need to cultivate reflexive mindsets plus the relevant skills needed to judiciously close the unavoidable gaps between guidelines and their application in concrete cases. This equally applies to the gaps which cannot be filled by reference to additional guidance from prior conceptual and empirical research in specific contexts. (shrink)