For this theme issue, "Reflections on the Revised Common Rule," we invited leading experts and scholars in research ethics to identify and comment on some of the important changes that the U.S. Department of Health and Human Services made to the Common Rule in a final regulation the agency released in January 2017. The authors draw on their experience as institutional leaders, members of national research ethics advisory bodies and institutional review boards, and scholars with deep knowledge of the ethical issues that human biomedical and behavioral research raises. Carl Coleman addresses some of the implications of the definitional ambiguities that remain in the revision, including the distinction between research and quality assessment and quality assurance activities. Barbara Bierer argues that the generalizable knowledge definition of research should not be the criterion for distinguishing research from clinical care. Holly Fernandez Lynch, Emily Largent, and Deborah Zarin raise important issues about what kind of research could be conducted on and with the consent forms that the revised Common Rule requires be posted on a publicly accessible website. And Suzanne Rivera identifies several concerns about the new blanket requirement that multisite studies cede authority to one single IRB to review the protocols for all the study sites.