The rise in antibiotic resistance poses one of the greatest challenges to public health and modern medicine. The roots of the dilemma are many - overzealous use of antibiotics clinical and agricultural settings, the departure of major pharmaceutical companies from antibiotic development ,and simple Darwinian evolution of microbes. Can we lift ourselves out of the hole that we have dug? Many ethical dilemmas must be acknowledged and confronted, such as balancing restrictions on individual liberty for the protection of the public health and the well being of future generations. We must also consider just and sustainable use of this precious resource tailored to the markedly differing economic and epidemiological situations across the globe with diverse health systems and variable antibiotic markets. Victor Nizet, MD describes the current challenges and potential paths forward. Recorded on 02/03/2021. (#36634)