This article describes the history of the Scientific Review Committee (SRC) for DSM-5 and reviews its background, procedures and deliberative processes, and conceptual/philosophical framework. The results of its work and the most important and contentious issues that arose in its efforts are reviewed. The central role of the SRC was to provide external review for all proposals for diagnostic change in DSM-5, evaluate them on their level of empirical support using objectively structured rules of evidence agreed upon in advance and make appropriate recommendations to the leadership of the American Psychiatric Association. While the creation of the SRC necessitated a great deal of additional work on the part of the SRC, the workgroups and the DSM-5 Task Force, the SRC succeeded in increasing the focus on empirical standards for nosologic change and providing a greater degree of consistency and objectivity in the DSM review process. The article concludes with recommendations, based on lessons learned, for similar efforts that might be included in future iterations of our psychiatric nosology.