Systems biology is increasingly popular, but to many biologists it remains unclear what this new discipline actually encompasses. This brief personal perspective starts by outlining the asthetic qualities that motivate systems biologists, discusses which activities do not belong to the core of systems biology, and finally explores the crucial link with synthetic biology. It concludes by attempting to define systems biology as the research endeavor that aims at providing the scientific foundation for successful synthetic biology.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.