The Young Foundation was commissioned by Nesta to explore how health information and knowledge might be affected by these trends. The Young Foundation and Nesta believe that the way knowledge is generated and applied in healthcare will change dramatically over the next decades, and has the potential to transform the way patients experience care, and how they make decisions about their own health. In this paper, we argue that society’s growing ability to mobilise knowledge from different fields and sources is beginning to show the potential of a ‘knowledge commons’ in healthcare: an open system of knowledge with researchers, practicing clinicians, patients, their families and communities all involved in capturing, refining and utilising a common body of knowledge in real time. A health knowledge commons has the potential to allow us to better understand and react to our own or another’s health in real time. It also has the potential to stimulate innovation in open science and academia, as access to different sources and new combinations of data generate new knowledge about the causes of disease. This paper contains four sections: firstly, we set out a brief architecture of a knowledge system and the different types of knowledge involved; secondly, we consider the issues with the creation and application of knowledge in the current system, involving healthcare providers, medical academia, patient–held and applied knowledge and considering how this interacts; thirdly, we look in more detail at some key trends mediated by technology, design, data management and presentation that have the potential to change how we orchestrate knowledge in health, with some examples; finally, we consider what this means for the development of a knowledge commons and the steps to get there.