Representative samples are required for ethical, valid, and useful health research. Yet, recruiting participants, especially from historically underserved communities, can be challenging. This paper presents findings from in-depth interviews with 40 mothers about factors that might influence their willingness to participate or allow their children to participate in medical research. Saliency analysis organizes the findings. Frequent and important salient themes about research participation included concerns that it might cause participants harm, hope that participants might gain a health benefit, and recognition that time and transportation resources could limit participation. Ultimately, we propose that a theoretical model, such as the Theory of Planned Behavior (TPB), will facilitate more systematic evaluation of effective methods for recruitment and retention of participants in medical research. Future research should explore the utility of such a model for development of effective recruitment and retention strategies.