Systems biology has been responsible for some of the most important developments in the science of human health and environmental sustainability. It is a holistic approach to deciphering the complexity of biological systems that starts from the understanding that the networks that form the whole of living organisms are more than the sum of their parts. It is collaborative, integrating many scientific disciplines – biology, computer science, engineering, bioinformatics, physics and others – to predict how these systems change over time and under varying conditions, and to develop solutions to the world’s most pressing health and environmental issues. This ability to design predictive, multiscale models enables our scientists to discover new biomarkers for disease, stratify patients based on unique genetic profiles, and target drugs and other treatments. Systems biology, ultimately, creates the potential for entirely new kinds of exploration, and drives constant innovation in biology-based technology and computation. Because systems biology requires constant attention to a very complex, very human social experiment, ISB fosters the kind of financial, social and psychological environment in which the world’s best scientists, technologists, engineers and mathematicians can collaborate and do their best work. A fundamental tenet of systems biology is that solving challenging biological problems always requires the development of new technologies in order to explore new dimensions of data space. New data types require novel analytical tools. This virtuous cycle of biology driving technology driving computation can exist only in a cross-disciplinary environment where biologists, chemists, computer scientists, engineers, mathematicians, physicists, physicians and others can come together in teams to tackle grand challenges. This is ISB. And this describes what we call the “innovation engine” (depicted below) that drives our ability to develop intellectual property, which we share through open-access platforms or by spinning out companies. In describing systems biology and the distinguishing characteristics of ISB’s approach, we always emphasize how our lab groups are intentionally and necessarily cross-disciplinary. One of our labs, for example, includes molecular biologists, microbiologists, geneticists, engineers, oceanographers, and even an astrophysicist. The complexity of biology in this age of “big data” requires diverse teams in order to tackle such vast amounts of data and to make sense of it all. New technologies that crunch data faster and more efficiently also permit researchers to re-analyze existing datasets, a process which often reveals undiscovered information. Complementary skills empower any of our groups of researchers to better understand biological or environmental challenges from different perspectives and to arrive at shareable insights more quickly. Our interdisciplinary teams have contributed notable advances to everything from ocean acidification to neurodegenerative diseases and tuberculosis to multiple cancers.