As telehealth plays an even greater role in global health care delivery, it will be increasingly important to develop a strong evidence base of successful, innovative telehealth solutions that can lead to scalable and sustainable telehealth programs. This paper has two aims: (1) to describe the challenges of promoting telehealth implementation to advance adoption and (2) to present a global research agenda for personalized telehealth within chronic disease management. Using evidence from the United States and the European Union, this paper provides a global overview of the current state of telehealth services and benefits, presents fundamental principles that must be addressed to advance the status quo, and provides a framework for current and future research initiatives within telehealth for personalized care, treatment, and prevention. A broad, multinational research agenda can provide a uniform framework for identifying and rapidly replicating best practices, while concurrently fostering global collaboration in the development and rigorous testing of new and emerging telehealth technologies. In this paper, the members of the Transatlantic Telehealth Research Network offer a 12-point research agenda for future telehealth applications within chronic disease management.