Background: Telegenetics is the provision of genetics services at a distance via telecommunication and information technologies. While telegenetics promises to increase access to underserved populations with rare diseases, providers must overcome additional challenges to reach remote and marginalized communities with telegenetics care provision. Method: We describe a series of case vignettes related to clinical care and barriers that were observed after using telegenetics in rural Appalachia. This geo-politically defined region is known for health disparities such as lower education levels, higher poverty levels, and greater healthcare shortage areas than the United States as a whole. Results: Although telegenetics improves access to care, the barriers experienced included (1) the digital divide in access to broadband, (2) telegenetics counseling in geriatric patients with limited computer literacy, (3) comorbidities that are common in the region, and (4) patients’ adherence to telegenetics services. Conclusion: These case studies emphasize the need for intervention studies to address implementation of telegenetics in populations who experience health disparities. In addition, future attention should also focus on administrative system evaluation and cost to reduce health disparities in disadvantaged groups.