Context: Decades of behavioral research suggest that awareness of health threats is a necessary precursor to engage in health promotion and disease prevention, findings that can be extended to the community level. Purpose: We sought to better understand local perspectives on the main health concerns of rural Appalachian communities in order to identify the key health priorities. While Kentucky Appalachian communities are often described as suffering from substandard health, resource, and socioeconomic indicators, strong traditions of community mobilization make possible positive, home-grown change. Methods: To assess what women, the key health gatekeepers, perceive as the most significant health threats to their rural communities, 10 focus groups were held with 52 Appalachian women from diverse socioeconomic backgrounds. Tape-recorded narratives were content analyzed and a codebook was developed. Measures designed to increase data trustworthiness included member checks, negative case evidence, and multiple coding. Findings: The following rank-ordered conditions emerged as posing the greatest threat to the health of rural Appalachian communities: (1) drug abuse/medication dependence; (2) cancer; (3) heart disease and diabetes (tied); (4) smoking; (5) poor diet/overweight; (6) lack of exercise; and (7) communicable diseases. These health threats were described as specific to the local environment, deriving from broad ecological problems and were connected to one another. Conclusion: Drawing on participants' community-relevant suggestions, we suggest ways in which rural communities may begin to confront these health concerns. These suggestions range from modest, individual-level changes to broader structural-level recommendations.