The war against bacteria, from the past to present and beyond.

Introduction: The human defense against microorganisms dates back to the ancient civilizations, with attempts to use substances from vegetal, animal, or inorganic origin to fight infections. Today, the emerging threat of multidrug-resistant bacteria highlights the consequences of antibiotics inappropriate use, and the urgent need for novel effective molecules.

Methods And Materials: We extensively researched on more recent data within PubMed, Medline, Web of Science, Elsevier's EMBASE, Cochrane Review for the modern pharmacology in between 1987 - 2021. The historical evolution included a detailed analysis of past studies on the significance of medical applications in the ancient therapeutic field.

Areas Covered: We examined the history of antibiotics development and discovery, the most relevant biochemical aspects of their mode of action, and the biomolecular mechanisms conferring bacterial resistance to antibiotics.

Expert Opinion: The list of pathogens showing low sensitivity or full resistance to most currently available antibiotics is growing worldwide. Long after the 'golden age' of antibiotic discovery, the most novel molecules should be carefully reserved to treat serious bacterial infections of susceptible bacteria. A correct diagnostic and therapeutic procedure can slow down the spreading of nosocomial and community infections sustained by multidrug-resistant bacterial strains.