Nature’s special issue probes how scientists and social scientists are coming together to solve the grand challenges of energy, food, water, climate and health. This special scrutinizes the data on interdisciplinary work and looks at its history, meaning and funding. A case study and a reappraisal of the Victorian explorer Richard Francis Burton explore the rewards of breaking down boundaries. Meanwhile, a sustainability institute shares its principles for researchers who work across disciplines. Thus inspired, we invite readers to test their polymathy in our lighthearted quiz.