The article presents a pilot project to sequence and analyze the genomes of 56 culturable species of Bacteria and Archaea, selected to maximize phylogenetic coverage. The goal is to explore the benefits of sequencing microbial genomes based on their evolutionary relationships rather than just physiological characteristics. The selected organisms were chosen based on their position in a phylogenetic tree of small subunit (SSU) ribosomal RNA genes, aiming to cover a broad range of bacterial and archaeal diversity. The analysis of these genomes demonstrated significant advantages in various areas, including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. The results highlight the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' to maximize the knowledge derived from microbial genome data. The authors estimate that sequencing the genomes of only 1,520 phylogenetically selected isolates could encompass half of the phylogenetic diversity represented by known cultured bacteria and archaea, and they suggest that this is a tractable target given the ongoing reductions in sequencing costs and complexity.The article presents a pilot project to sequence and analyze the genomes of 56 culturable species of Bacteria and Archaea, selected to maximize phylogenetic coverage. The goal is to explore the benefits of sequencing microbial genomes based on their evolutionary relationships rather than just physiological characteristics. The selected organisms were chosen based on their position in a phylogenetic tree of small subunit (SSU) ribosomal RNA genes, aiming to cover a broad range of bacterial and archaeal diversity. The analysis of these genomes demonstrated significant advantages in various areas, including the reconstruction of phylogenetic history, the discovery of new protein families and biological properties, and the prediction of functions for known genes from other organisms. The results highlight the need for systematic 'phylogenomic' efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and Archaea' to maximize the knowledge derived from microbial genome data. The authors estimate that sequencing the genomes of only 1,520 phylogenetically selected isolates could encompass half of the phylogenetic diversity represented by known cultured bacteria and archaea, and they suggest that this is a tractable target given the ongoing reductions in sequencing costs and complexity.