Today, researchers, enterprise owners, and policy makers are working together in haste to understand and manage human influence on resources of the high seas. The oceans represent one-and-a-half times the total land area on the planet and their dynamics play critical yet poorly understood roles in regulating climate and biogeochemical cycles, supporting biodiversity, and providing rare habitats to rare species. At the same time, development of ocean resources is moving forward at breakneck pace, putting the sustainable health of the high seas at risk. This Special Collection on the Science of the High Seas brings together a powerful set of ground-breaking research articles to help scientists and policymakers better understand ecological, geological, and other systems that underlie the functional health of global oceans, and inform those concerned with the exploration and use of living and mineral resources. The data and analyses in this collection highlight the challenges in balancing the long-term imperatives of preserving global ocean resources with shorter-term economic and political interests that seek to quickly and vigorously draw value from them.