Single-case research design (SCRD) studies can provide the methodological flexibility that is needed to develop and examine educational interventions in ways that can consider and describe the influence of setting variables on intervention outcomes. The authors of this article share recommendations for conducting SCRD studies in ways that may help to generate research information that meaningfully supports rural education policy and practice. Their recommendations for SCRD researchers who examine rural settings include (a) promoting studies that show diminished intervention effects or difficulties with experimental control in rural areas, (b) using flexibility when selecting and using single-case design and reporting guidelines, (c) using established locale classification systems and comprehensively describing the setting and participants, (d) including local constituents as research partners, and (e) using an open science registry.