From its inception, the field of Mind, Brain, and Education (MBE) has been conceived as an interdisciplinary science, and with good reason: The phenomena the field aims to understand often arise from interactions among multiple factors, span levels of analysis, and are context dependent. In this article, we argue that to reach its potential as an interdisciplinary science—and in order to explain such complex phenomena—MBE must be fundamentally organized around meaningful, discipline-spanning questions, and the questions must determine tools and research methods (not the other way around). Using examples from three central questions in MBE—“who,”“when,” and “how”—we highlight the limits of single disciplines, and the value of a question-driven interdisciplinary approach in MBE, with respect to questions that can be asked, the perspectives that can be considered, and the array of methods, tools, and models that can be made available. We believe that the future is bright for MBE, and that the field has a unique opportunity to provide meaningful answers to some of the most difficult questions in education today. However, realizing this potential depends on, as a first step, allowing the questions themselves to drive the field's work moving forward.