The major goals of telemedicine today are to develop next-generation telehealth tools and technologies to enhance healthcare delivery to medically underserved populations using telecommunication technology, to increase access to medical specialty services while decreasing healthcare costs, and to provide training of healthcare providers, clinical trainees, and students in health-related fields. Key drivers for these tools and technologies are the need and interest to collaborate among telehealth stakeholders, including patients, patient communities, research funders, researchers, healthcare services providers, professional societies, industry, healthcare management/economists, and healthcare policy makers. In the development, marketing, adoption, and implementation of these tools and technologies, communication, training, cultural sensitivity, and end-user customization are critical pieces to the process. Next-generation tools and technologies are vehicles toward personalized medicine, extending the telemedicine model to include cell phones and Internet-based telecommunications tools for remote and home health management with video assessment, remote bedside monitoring, and patient-specific care tools with event logs, patient electronic profile, and physician note-writing capability. Telehealth is ultimately a system of systems in scale and complexity. To cover the full spectrum of dynamic and evolving needs of end-users, we must appreciate system complexity as telehealth moves toward increasing functionality, integration, interoperability, outreach, and quality of service. Toward that end, our group addressed three overarching questions: (1) What are the high-impact topics? (2) What are the barriers to progress? and (3) What roles can the National Institutes of Health and its various institutes and centers play in fostering the future development of telehealth?