Transforming natural helpers into lay health advisors (LHAs) is a complex undertaking. Using the North Carolina Breast Cancer Screening Program (NC-BCSP) as a case study, this article describes the steps involved in developing, implementing, and evaluating an LHA intervention, considering factors that make the LHA approach appropriate for the NC-BCSP's population, setting, and health focus. The authors review five phases of implementation (start-up, training, LHA activities, follow-up, resource mobilization) and discuss the NC-BCSP's evaluation strategies and tools in light of difficulties involved in assessing natural helping processes and impact. Program challenges related to resource needs, identification of natural helpers, and LHA monitoring and support also are considered. The authors describe ways in which one large group of older, rural, African American LHAs are helping establish countywide partnerships between health care providers, agencies, and local communities that support and sustain individual changes in health behavior.