Increasing our understanding of Earth’s biodiversity and responsibly stewarding its resources are among themost crucial scientific and social challenges of the new millennium. These challenges require fundamentalnew knowledge of the organization, evolution, functions, and interactions among millions of the planet’sorganisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biologythat aims to sequence, catalog, and characterize the genomes of all of Earth’s eukaryotic biodiversity over aperiod of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, suchas the impact of climate change on biodiversity, the conservation of endangered species and ecosystems,and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces,including data-sharing policies that ensure a permanent, freely available resource for future scientific dis-covery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describescientific and organizational challenges in executing such an ambitious project, and the structure proposedto achieve the project’s goals. The far-reaching potential benefits of creating an open digital repository ofgenomic information for life on Earth can be realized only by a coordinated international effort.