National Institutes of Health (NIH) director Elias Zerhouni is pushing hard for innovation and the risk taking required to make major leaps in medicine. Fully attuned to cutting-edge work that crosses disciplines, he cites nanotechnology, clinical databases designed to answer research questions, systems biology, and an openness to radical ideas among his top priorities. The NIH director's job, he says, "is to have a vision." This requires leveraging NIH funding so that money is spent more wisely and has a cumulative effect on population health. Knowledge can be extracted from science, and health system transformation is made possible.