Special education researchers have indicated the need for an increased use of mixed methods research to address many of the complex issues in the field. An important first step in designing mixed methods research is to develop quality research questions. The aim of this article is to provide fundamental information on the formation of mixed methods research questions. Four interconnected topics are presented that will help researchers to conceptualize mixed methods special education research questions. First, a discussion is provided on how to select research methods based on the overall purpose of a study. Information is presented on the importance of keeping students with disabilities a central focus of the research questions. Next, the relevance of using suitable measurement instrumentation is discussed. Issues related to quantitative research (validity), qualitative research (credibility, trustworthiness), and mixed methods research (legitimization, meta-inferencing) are presented. Third, the importance of allowing for a theoretical lens that considers the continuum between qualitative and quantitative is highlighted. Establishing a balance between qualitative and quantitative perspectives has the potential to build upon the strengths of both research methodologies. Finally, a discussion on the integration of the first 3 topics as a means of developing high-quality, relevant research questions is offered. Across the 4 topics, examples from special education research are provided.