Antibiotic resistance is one of the most significant challenges to the health care sector in the 21st century. A myriad of resistance mechanisms have emerged over the past decades and are widely disseminated worldwide through bacterial populations. At the same time there have been ever fewer new antibiotics brought to market, and the pharmaceutical industry increasingly sees antibiotics as a poor investment. Paradoxically, we are in a Golden Age of understanding how antibiotics work and where resistance comes from. This knowledge is fueling a renaissance of interest and innovation in antibiotic discovery, synthesis, and mechanism that is poised to inform drug discovery to address pressing clinical needs.