Our Healthcare systems worldwide are facing grand challenges that can be addressed by intelligent, miniaturized and interconnected devices. Many of today's pharmaceutical drugs create bigger problems than solutions, as drugs help only 40% of the patients and kill, in the USA alone, over 100,000 people per year. The widespread use of antibiotics has led to new strands of bacteria that defy all known antibiotics and kill well over 100,000 people yearly in the world. Outbreaks of infections by new viruses and anti-resistant bacteria are expected with even more grave consequences. The quality of food around the world is steadily deteriorating, as the soils are becoming depleted of essential nutrients and contain increasing amounts of pesticides, herbicides and fungicides. Our environment is burdened with 2.5 billion tonnes of chemicals per year that accumulate in the soil, groundwater, rivers and seas, and eventually end up in our food and our drinking water. As a consequence, there is a strong increase in the incidence of diseases hardly known fifty years ago. In parallel, an increasing number of people are taking the responsibility for their health and well-being in their own hands and are looking for mobile and in-obtrusive ways to objectively monitor their health status. The development of intelligent, miniaturized systems, by the heterogeneous integration of technologies such as micro- and nano-electronics, photonics, biotechnology, materials and information & communication, addresses these issues and has received intensive public support in the EU over the past two decades in the FP6 and FP7 programs. Proven concepts and functional prototypes exist with the potential to create new opportunities to improve our healthcare systems, in particular personalized or precision medicine. These device concepts offer unique abilities to sense, detect, analyze, communicate, respond, and monitor phenomena from the macro (e.g. body, tissues) to the nano scale (e.g. molecules, genes) on the spot, with short response times. For the majority of the projects, the planning for the next phase of prototype validation, through product design, supply chain setup, user targeting, clinical validation and commercial roll-out is now taking full attention. However, significant hurdles exist in the successful translation of the new technology to new products. As these technologies are new-to-the-world the resulting products carry a high risk, often necessitating the creation of new companies. Therefore the EU has developed the Horizon 2020 program as a framework for technology development and new business creation. Horizon 2020 is focusing on support for technology transfer, and on building ecosystems and value chains to ensure shorter times-to-market, thus enabling a higher impact of knowledge-based technologies. This paper will argue the necessity of developing these new class of devices, discuss its state-of-the-art, and the challenges for the implementation of Horizon 2020 and the new opportunities in intelligent miniaturized systems for pHealth.