The Institute for Informatics (I2) is a comprehensive home for biomedical informatics and data science research, education and services spanning Washington University, BJC HealthCare and affiliated entities. It was created in response to the changes currently being experienced across the modern healthcare and life sciences environments. There has been a fundamental shift towards trans-disciplinary, integrative and data-intensive approaches to basic, clinical, translational and population level research. These developments have been coupled with the widespread use of information technology platforms to re-engineer healthcare delivery and achieve greater value alongside improved outcomes and safety. The complex data, information and knowledge needs associated with these trends requires a comprehensive and systems-level approach to biomedical informatics and data science research, education and practice.