Bacterial cell wall (peptidoglycan) is one of the most successful targets for antibiotic intervention. Nowadays, when we face an unprecedented rise of multidrug resistant bacteria, cell wall active antibiotics remain the line of last defense. Humankind desperately needs new classes of antibiotics to avoid the disasters of pre-antibiotic era, and much effort is spent to develop novel compounds that act on peptidoglycan. In my talk I will present the use of molecular phylogenetic approaches  to elucidate the evolution of genes for two important classes of peptidoglycan inhibitors, glycopeptides and moenomycins.  Prospects of use of obtained insights for screening and generation of novel antibiotics will be outlined.