In 2002, the National Research Council (NRC) released Scientific Research in Education, a report that proposed six principles to serve as guidelines for all scientific inquiry in education. The first of these principles was to “pose significant questions that can be investigated empirically” (p. 3). The report argued that the significance of a question could be established on a foundation of existing theoretical, methodological, and empirical work. However, it is not always clear what counts as a significant question in educational research or where such questions come from. Moreover, our analysis of the reviews for manuscripts submitted to JRME1 suggests that some practical, specific guidance could help researchers develop a significant question or make the case for the significance of a research question when preparing reports of research for publication.