In the course of his exceptional career, Lee Hood has lived through, and helped in significant ways to catalyze, four major paradigm shifts in biology (i.e., the joining of engineering to biology, the human genome project, cross-disciplinary biology and, of late, systems biology). Together, he explains, they have brought us to the threshold of the next great shift, dubbed P4 by Hood, the transition from descriptive to informational, from reactive to – and here’s where the P comes in – proactive, medicine. (The 4 stands for predictive, personalized, preventive and participatory.) Within a decade, he says, thanks to systems approaches to disease, powerful new-to-the-scene synthesizing and sequencing technology and the computational and mathematical tools that lie at the heart of P4, researchers will have the wherewithal to convert the virtual cloud of billions of data points that will surround each patient into simple hypotheses about health and disease and, with that, dramatically transform the practice of healthcare as we know it.