Despite vast amount of money and research being channeled toward biomedical research, relatively little impact has been made on routine clinical practice. At the heart of this failure is the information and communication technology “chasm” that exists between research and healthcare. A new focus on “knowledge engineering for health” is needed to facilitate knowledge transmission across the research–healthcare gap. This discipline is required to engineer the bidirectional flow of data: processing research data and knowledge to identify clinically relevant advances and delivering these into healthcare use; conversely, making outcomes from the practice of medicine suitably available for use by the research community. This system will be able to self-optimize in that outcomes for patients treated by decisions that were based on the latest research knowledge will be fed back to the research world. A series of meetings, culminating in the “I-Health 2011” workshop, have brought together interdisciplinary experts to map the challenges and requirements for such a system. Here, we describe the main conclusions from these meetings. An “I4Health” interdisciplinary network of experts now exists to promote the key aims and objectives, namely “integrating and interpreting information for individualized healthcare,” by developing the “knowledge engineering for health” domain. Hum Mutat 33:797–802, 2012. © 2012 Wiley Periodicals, Inc.