High rates of sexually transmitted diseases (STDs) are sustained in communities by a relatively small group of people, referred to as the core of transmission. Definitions of the core vary but inevitably include people who are socially marginalized and who distrust people in authority, such as public health practitioners and university researchers. Having an effect on a marginalized group usually depends on effective collaboration with people they trust. Researchers from the University of North Carolina School of Public Health developed a trust-based collaboration with community members of a rural county in North Carolina to implement an STD prevention program that, in turn, relied on trust in local social networks. As part of the STD prevention demonstration project, the research team established a community resource group made up of local African Americans who helped design, implement, and evaluate the intervention. The group identified 21 women to whom others in the community turned for advice on sex and STDs. These women were trained as lay health advisors to disseminate information and skills for preventing STDs among their social networks. Through face-to-face structured interviews before and after the intervention, the authors measured improvements in STD treatment and prevention behaviors. The proportion of people practicing each of the targeted behaviors improved during the evaluation period. In addition to disseminating information through their own social networks, the lay health advisors demonstrated new skills and a desire to interact with local care providers to influence the provision of care for STDs for low-income African Americans in this county. Each participant in the collaboration played a role in establishing or building upon trust with others. These trusting relationships were critical for empowering a marginalized group at high risk for STDs.