Historically, therapies have been set up empirically with some undeniable success. Yet, this is only with the detailed understanding of diseases’ mechanisms that tailored and precision therapies have been developed. For example, the deciphering of the basic mechanisms of virus replication and oncogenic signaling, have led to the development of highly effective and extremely specific antivirals and anti-tumor therapies, respectively. In the field of antibacterial therapy (antibiotics), chemical substances targeting bacterial specific components like peptidoglycan have been discovered, such as beta lactams and glycopeptides. Yet, while their selectivity for bacteria is high, the intended pathogen is not the only target, also is the microbiota. This has two detrimental consequences: the selection and amplification of antimicrobial resistant pathogenic and commensal bacteria, and the blocking of the beneficial effects on the host of the microbiota. Antimicrobial resistance continuous expansion, and the recognition of the detrimental effects of broad spectrum antimicrobial therapy on beneficial bacteria therefore call for an urgent strategical and tactical change in antimicrobial therapy: there is a need for drugs that either specifically target pathogenic microbes or/and block their pathogenic mechanisms. The development of these new therapeutic strategies requires a detailed and complete understanding of basic microbiology and infectious diseases mechanisms. Funding basic research in microbiology and pathogenesis is the way forward to combat resistance to antibiotics.