Over the past decade, awareness emerged that existing frameworks for regulation and oversight of research with human participants fit poorly with contemporary research. Although substantial and diverse literature touches on this dissonance from a variety of perspectives, the problem is illustrated most clearly by the 2011 to 2017 process undertaken to “modernize” the Common Rule, the federal regulations for the protection of human research subjects. During this process, the Office for Human Research Protections (OHRP) sought public comment on a wide array of challenges they felt were not addressed adequately in existing regulations, and that they hoped to address in proposed revisions. The most widely debated proposal aimed to address a perception that a long-standing policy allowing the research use of nonidentified biospecimens without informed consent no longer made sense given the potential of genomic technologies to reidentify such samples.1 OHRP, recognizing concerns that existing regulations created undue burdens on very low-risk research, also proposed a plan to allow investigators to use a decision tool to determine whether a study would be “excluded” from IRB review. Proposals intended to address these and other concerns prompted critiques in the scholarly literature and in comments submitted to OHRP during the public comment period. Ultimately, the most controversial proposals, including requiring informed consent for nonidentified biospecimens research, were not part of the final rule published in January 2017 on the final day of the Obama administration. Two years after it was published, this final rule was implemented in January 2019. As leaders of a multi-disciplinary team working on the ethical and regulatory challenges raised by biorepository research in multi-site networks, we believe that both the controversy surrounding the OHRP proposals and the modest outcome of this six-year process are symptoms of a larger challenge. The regulatory revision process initiated by OHRP focused primarily on the transformation of biomedical science. Critically, however, it did not adequately consider the transformation that has occurred with regard to cultural perspectives on a range of critical issues relevant to the oversight of research with human subjects. These include, but are not limited to: changing perspectives on the right to privacy (and limits thereto), power imbalances between experts and lay people, trust in institutions, and individual ownership and control of data and biomaterials. OHRP, and the biomedical research community at large, have not resolved important questions about the oversight of human subjects research because we have not sufficiently accounted for the ways that society and societal norms have shifted since the Belmont Report was published 1979 and 45 CFR 46 Subpart A (what we now call the Common Rule) was adopted in 1981. It is time to undertake a different strategy for working toward the modernization of oversight and governance of research with humans. First, we need to revisit the principles articulated in the Belmont Report. If we aim to settle on an ethical framework that supports the development of policies, what ethical commitments and ideas must be included? Are additional ethical principles needed to ground this effort? Second, we need to conduct empirical research and public engagement activities to understand the views of diverse stakeholders on the ethical basis for policies on human subjects research. What implications do the Belmont principles hold for us today? Third, we need a process whereby this more contemporary interpretation of principles to guide human research ethics can be translated into policy and practice, with a focus that extends beyond the Common Rule to take a more comprehensive and global view of research oversight and governance. This work would recognize that changing societal contexts calls for changing approaches to process: a repeat of the original Belmont process would be an anachronism. While the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research successfully developed the original Belmont Report, it no longer makes sense for a small and distinguished group of scholars to gather at a conference center over a three-year period. Our proposal emphasizes a more transparent and inclusive – and thus more “modern” – process.