Our understanding of the world—even our well-being—is shaped by advances in basic science knowledge. Philanthropic organizations play a crucial role in supporting the research that leads to such advances. For example, they support scientists, build organizations' research capacity and help train new generations of scientists. Philanthropies making such investments in basic or discovery science share a common goal—to catalyze advances in knowledge that improve our lives by enhancing our understanding of ourselves, our world and our universe. They also share a common challenge: establishing that their investments in basic science indeed contribute to advancing knowledge. This brief summarizes learning from early efforts by a working group of philanthropies and other organizations that are tackling this challenge together.