Integrating knowledge from the molecular and social sciences has become an important avenue toward understanding how social experience becomes biologically embedded to affect health adversely over the life course in marginalized populations. Conducting rigorous and deeply integrated biopsychosocial research is complicated by practical and ethical challenges. In particular, identifying and successfully recruiting study participants from marginalized communities for sociological research poses unique challenges, and these challenges are exacerbated when the research efforts include collection of biological samples. Our dynamic and contingent theoretical understanding of how socially structured experiences become biologically embedded to activate population health inequities—the weathering hypothesis—led us to focus this study on a single economically depressed city, Detroit, Michigan, rather than a national sample and to apply community-based public health principles to collect biological data from residents. We found linking to an established community-based partnership between our university and Detroit community partners was the first, but far from the last step to successfully collecting biological specimens from a diverse, low-income, and historically exploited set of participants. The purpose of this case study is to share the lessons learned from our research experience and provide a set of practical guidelines for collecting biological data from an ethnically and racially diverse economically depressed urban community.