In accordance with the recent revision of the Common Rule (Subpart A of the U.S. Department of Health and Human Service’s regulations for the protection of human subjects in research at 45 CFR 46), the use of single IRB has become mandatory for cooperative research in the U.S. Thus, interest has grown in operating alternative IRB models, including central IRBs and/or joint IRBs. However, since the single IRB mandate has risks as well as benefits, such revision should be carefully considered before adopting it. Accordingly, this study examined the institutional changes and progress of the U.S. research ethics review system, the efforts that have been made to avoid inefficiencies caused by duplicate reviews for multi-center cooperative research, and the single IRB-related policies and regulations that have been enacted or revised thereafter. Additionally, this study compared the differences between the regulations and guidelines in the Korean Good Clinical Practice (KGCP) and those in the Bioethics and Safety Act. On the basis of this examination, it is argued that before a single IRB review model is adopted in Korea, it is necessary for all relevant parties to conduct a full review of the current responsibilities of researchers and institutions under existing laws and regulations and to determine how those responsibilities would be shared in the event of a single IRB review model.