There is a growing acceptance of the utility of mixed methods in health sciences but there is no widely accepted set of ideas with regard to use of a conceptual or theoretical framework to guide inquiry. Few mixed methods health science articles report the use of such a framework. Lack of available conceptual maps provided by theoretical frameworks, necessary intricacy of design, and the qualitative “black box” tradition all contribute to a dearth of methodological guidance in such studies. This article uses a funded National Institutes of Health study as an example to explain the utility of a theoretical framework in conceptualizing a study, making design decisions such as sampling and recruitment, collecting and analyzing data, and data interpretation.