Single-case designs are typically used in classroom and clinical settings to assess the behavioral impacts of an intervention with an individual child. Using two illustrative case studies, this article describes the extension of this model to home-visitation programs serving tribal communities and examines the lessons learned throughout the process of adapting this approach. Our experience suggests that the benefits of using this design outweigh the associated challenges and allows researchers to expand the use of single-case designs to previously unexplored settings. Specifically, some of the benefits discussed include allowing for evaluative rigor in contexts with small samples, allowing everyone who qualifies to immediately participate, providing visual representations of the outcome-making the results more tangible and accessible to a broader audience, and allowing for a deep level of cultural sensitivity. The article also provides some general guidelines to address the practical challenges one may face when attempting to use single-case designs in novel ways within nonschool settings.