Today, everything is affected by the digital revolution – the impact of new technology on improving the health and well-being of individuals, communities, and populations is unprecedented. Recent technological achievements have revolutionized clinical practice, from prevention through diagnosis, monitoring to disease management, and enabled unprecedented public interest and engagement in self-management and well-being. Digital health is defined as the “use of information and communications technologies to improve human health, healthcare services, and wellness for individuals and across populations.” Dozens of digital health projects have been conducted in Europe alone (1) and with the growth of mobile technology for improving health and well-being (mHealth). There is an unprecedented opportunity to transform the healthcare sector and empower citizens in taking charge of their own health (2). However, the successful development, integration and implementation of new technology and methods require a radical shift from traditional and single-disciplinary academic and clinical approaches. In order to truly embrace these opportunities and transform healthcare and improve well-being, we need a new approach to science and health research. Only when investigated together, aimed at solving real-world problems, will health and technology be in a position to create results with significant impact on the delivery of clinical and social care and improve the well-being of individuals and populations. First, recent technological advances enabled by the creation of real-time big data streams, social media, and infectious disease modeling are the focus of public health computer science, aiming to strengthen disease surveillance, early-warning, preparedness, and response through integration of traditional surveillance systems with new big data sources. Second, advances in reliability and accuracy of medical devices and personalized technology, together with booming wearable and tracking technology (MedTech), have rapidly become established as the mainstream enhancing opportunities for personalized care, improving self-management, and bringing the desirable outcome: behavior change. Third, with over 4.55 billion people worldwide using a mobile phone in 2014, mHealth apps and interventions empower users in the developed world and are accelerating unprecedented access to best evidence and healthcare service in the low and middle income settings. Fourth, more than a decade ago, Sir Muir Gray forecasted that “knowledge is the best enemy of disease – the application of what we know already will have a bigger impact on health and disease than any drug or technology likely to be introduced in the next decade” (3). Better use of technology for capturing, understanding, and disseminating knowledge is paramount for fulfilling this vision. The recent research achievements in web science, data mining and analytics, medical ontologies, and recommender systems provide further opportunities for better evidence dissemination, medical advice, and development of personalized persuasive intelligent systems. Fifth, serious games for health- and game-based learning have crossed the rubicon from entertainment technology to education and health interventions, and are getting firmly established as health educational and intervention tools. Finally, in light of the speed of data sharing technologies and the absence of a legal framework, we must engage in policy debates safeguarding individual privacy, regulation usage of data for commercial purposes, while enabling transparent data sharing for research. However, these challenges are only achievable through truly multi-disciplinary research collaborations.