The study by Glass et al. identifies essential genes in *Mycoplasma genitalium*, a bacterium with the smallest known genome capable of independent growth. Using global transposon mutagenesis, the researchers isolated and characterized mutants for 100 nonessential protein-coding genes, none of which were RNA-coding genes. They identified 382 of the 482 protein-coding genes as essential and found five sets of genes encoding proteins with redundant essential functions, such as phosphate transport. Genes encoding proteins of unknown function accounted for 28% of the essential protein-coding genes. Some gene disruptions accelerated *M. genitalium* growth, while others slowed it. The findings suggest that *M. genitalium* has a minimal set of genes necessary for bacterial life, with some apparent enzymatic redundancy. The study also highlights the importance of hypothetical and unknown function proteins in essential pathways.The study by Glass et al. identifies essential genes in *Mycoplasma genitalium*, a bacterium with the smallest known genome capable of independent growth. Using global transposon mutagenesis, the researchers isolated and characterized mutants for 100 nonessential protein-coding genes, none of which were RNA-coding genes. They identified 382 of the 482 protein-coding genes as essential and found five sets of genes encoding proteins with redundant essential functions, such as phosphate transport. Genes encoding proteins of unknown function accounted for 28% of the essential protein-coding genes. Some gene disruptions accelerated *M. genitalium* growth, while others slowed it. The findings suggest that *M. genitalium* has a minimal set of genes necessary for bacterial life, with some apparent enzymatic redundancy. The study also highlights the importance of hypothetical and unknown function proteins in essential pathways.