We ask if it’s possible to accelerate the advancement of science by applying the science of science to the frontiers of knowledge. Using a robot scientist as an example, we show how it is now possible to close the loop by building machines that can create scientific knowledge. We discuss the implications of this on the future of the discipline. Another way to more efficiently advance science is to generate more fruitful hypotheses. We discuss the Swanson hypothesis, which provides a window into how to hone in on valuable discoveries, allowing for the forecasting of frutiful areas of research. We then explore how the frontiers of science can be traced, allowing scientists to more thoughtfully choose topics that will accelerate collective discovery. Finally, we address some challenges posed by this issue, including the “file drawer problem,” which could be mitigated by a more systemic approach to sharing negative results with colleagues in the discipline. We suggest several ways to incentivize and reward impactful science so that we can efficiently reap its benefits.