Yeasts offer a unique opportunity to understand the genetic mechanisms that generate biodiversity. Their remarkably diverse heterotrophic metabolisms have allowed them to partition nutrients in every major aquatic and terrestrial biome and to inhabit every continent. They have evolved radically different carbon metabolisms and energy management strategies. Most yeasts prefer respiration, but some species, such as the genetic model system Saccharomyces cerevisiae, have evolved highly fermentative lifestyles. A handful of clades can accumulate over half of their dry weight as fatty acids, while several species can ferment pentose carbon sources, such as xylose, which is the second most-abundant sugar in plant biomass. The Y1000+ Project (http://y1000plus.org) seeks to determine the genetic basis of yeast metabolic diversity across the subphylum Saccharomycotina. Here we report progress on generating and analyzing functionally annotated genome sequences for all ~1,000 known species of yeasts, as well as comparing their genome contents with rich functional, ecological, and metabolic data. By creating and analyzing the first comprehensive genomic dataset and catalog of metabolic diversity for a high-level taxonomic rank, the Y1000+ Project will illuminate how key genetic innovations and convergent genetic changes have driven diversification across half of billion years of evolution. Comprehensive taxon and genome sampling will allow us to determine how metabolic diversity is encoded in their genomes; the tempo and mode of change; and which phenotypic traits and genetic changes lead to niche expansion, clade diversification, and long-term survival. The genetic features that cause some yeasts to brew beer, others to proliferate on cacti, and still others to blight crops or cause lethal infections are gradually coming into focus.