Antibiotic resistance is undoubtedly one of the greatest challenges to global health, and the emergence of resistance has outpaced the development of new antibiotics. However, investments by the pharmaceutical industry and biotechnology companies for research into and development of new antibiotics are diminishing. The public health implications of a drying antibiotic pipeline are recognized by policymakers, regulators and many companies. In this Viewpoint article, seven experts discuss the challenges that are contributing to the decline in antibiotic drug discovery and development, and the national and international initiatives aimed at incentivizing research and the development of new antibiotics to improve the economic feasibility of antibiotic development. In this Viewpoint article, seven experts discuss the challenges that are contributing to the decline in antibiotic drug discovery and development, and the international and national initiatives aimed at incentivizing research and the development of new antibiotics to improve the economic feasibility of antibiotic development. Christine Ardal co-leads research and innovation in the European Union Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections. Previously she was the co-lead on incentives to stimulate antibacterial innovation for the European Union’s DRIVE-AB project. She is a senior adviser at the Norwegian Institute of Public Health, where her research and policy work focuses on medicine innovation, access and stewardship. Manica Balasegaram trained as a medical doctor at the University of Nottingham, United Kingdom, and from 2001 onwards worked as a doctor and researcher in several countries in sub-Saharan Africa and southern Asia with Medecins Sans Frontieres. In 2007, he joined the Drugs for Neglected Diseases initiative as Head of the Leishmaniasis Clinical Program before returning to Medecins Sans Frontieres as Executive Director of the Access Campaign. He joined the Global Antibiotic Research and Development Partnership in June 2016, and is a board member of the Medicines Patent Pool as well as FIND’s Scientific Advisory Committee. He is also the executive director of GARDP. Ramanan Laxminarayan is the founder and Director of the Center for Disease Dynamics, Economics & Policy in Washington, DC, United States, and a senior research scholar at Princeton University. He is a voting member of the US Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. David McAdams is a game theorist and professor of economics in the Fuqua School of Business and Economics Department at Duke University, United States. His current research focuses on the economic epidemiology of information, with applications from antibiotic resistance to ‘fake news’. Kevin Outterson is a professor of law and N. Neal Pike Scholar in Health and Disability Law at Boston University, United States, and Executive Director of CARB-X. He has grappled for a dozen years with issues peculiar to antibiotic research and development, especially relating to intellectual property, reimbursement and business models. He now leads the world’s largest push incentive for antibacterial research and development, CARB-X, with a 5-year budget exceeding US$500 million. The views expressed herein are personal, and do not necessarily represent the views of CARB-X or any CARB-X funder. John H. Rex is a physician and drug developer with more than 30 years of development and policy experience focused on antimicrobial agents. He is currently Chief Medical Officer of F2G Ltd (an antifungal biotechnology company), an expert-in-residence for the Wellcome Trust and an operating partner with a venture capital group (Advent Life Sciences) and was (2015–2019) a voting member of the US Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. He blogs regularly at http://amr.solutions/blog.html. Nithima Sumpradit is a pharmacist and lead coordinator for development and implementation of Thailand’s National Strategic Plan on Antimicrobial Resistance 2017–2021. She is also a programme manager of the Royal Thai Government–WHO Country Cooperation Strategy Programme on Antimicrobial Resistance.