Earth is in the midst of a global biodiversity crisis, with species loss at 100 to 1,000-fold above the background extinction rate. Loss of biodiversity threatens vital ecosystems on which humans depend. In response to this crisis, the Earth BioGenome Project (EBP) was launched in 2018. The EBP aims to sequence, catalog and characterize the genomes of all of Earth’s known plant, animal and microbial eukaryotic biodiversity—approximately 1.8 million species. The ultimate aims of the EBP are to create a foundation for revealing the “rules of life” and delineate the mechanisms of how biological systems evolve under changing environmental conditions. This lecture will present recent progress made by the EBP and the challenges faced in reaching the project’s goals.