Arkansas's telemedicine system has evolved since 2003 from a support mechanism for high-risk pregnancy consultations to an initiative that spans medical specialties, including asthma care, pediatric cardiology, gynecology, and mental health. The system has also expanded care to diverse populations, including incarcerated women and people with HIV/AIDS. This article describes the system's evolution, organization, and diverse activities. It also shows how telemedicine can have a positive impact on a rural state and how such a state can become an engine for change regionally. The Arkansas telemedicine system faced classic challenges to uptake and function, in building and sustaining funding, in obtaining insurance reimbursement for services, and in educating patients and providers. The system's impacts on health outcomes and medical practice culture have also reached beyond patient care and provider support. The existing yet continually evolving telemedicine infrastructure and partnerships in Arkansas will respond to the state's inevitable health care reform adaptations from the Affordable Care Act and could provide direction for other states seeking to adopt or expand their telemedicine efforts. © 2014 Project HOPE- The People-to-People Health Foundation, Inc.