Antimicrobial resistance (AMR) is widespread. Its global human and economic burden is tremendous and increasing annually. Yet today only a few pharmaceutical companies retain active antibacterial drug discovery programmes. While the elaboration of antibiotics with novel mechanisms of action is scientifically complex, the chief challenge is diminishing incentives. Pre-market regulatory requirements and increased control on post-market access, use, and pricing of new antibiotics are strong deterrents to drug development. Meanwhile, healthcare payers are not currently prepared to reimburse antibiotics at prices that would support the cost of development.Applied to antibiotics, a simple sales-based economic model contradicts the public health mandate to reduce their consumption in order to preserve their efficacy. Alternative models that can create incentives for the discovery of novel antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue.The multidisciplinary and multi-stakeholder DRIVE-AB consortium composed of 16 public and 8 private partners from 12 countries will produce new models in a stepwise yet interconnected process. To achieve this objective, the DRIVE-AB consortium has put together a strong team that comprises both currently active researchers on the antibiotics problem and new researchers who can bring a fresh perspective as well as experience from other industries, economic specialties, and business cultures. The academic team has been enriched by EFPIA members and stakeholders from various backgrounds. With this diverse, yet closely tied team, DRIVE-AB will deliver fresh, sustainable solutions to this complex problem.First, we will develop an evidence-based, consensus definition for “responsible antibiotic use,” which, with its standardised quality and quantity indicators, will provide the framework for all later steps. Next, data from surveillance systems, antibiotic prescription databases, and published literature will inform estimations of the present burden of antibiotic resistance from both clinical and economic perspectives across varying socioeconomic backdrops. Simulation models informed by these data as well as data from past and ongoing epidemics will estimate future public health needs and impact related to AMR, again in diverse socioeconomic settings. Together these constructs will allow for valuation models that will estimate the true value of existing and new antibiotics from the perspectives of patients, physicians, payers, and society as a whole. These, in turn, will inform the creation of alternative economic strategies and reward models that will promote and sustain the development of new antibiotics while simultaneously bolstering appropriate use of existing antibiotics. The most promising schemes will be presented to policymakers and other stakeholders with attendant implementation and risk-management strategies.This ambitious project will not succeed if it is developed and championed merely by one sector of society, be it academia, “big pharma,” or public health. The robustness and applicability of the proposed alternative models will only be proportional to their level of input from all involved players. All work from beginning to end will be performed in close collaboration with the consortium’s stakeholder partners, which run the gamut from patients and clinical societies to small- and medium-sized enterprises, large pharmaceutical companies, healthcare payers, public health officials, and government officials. The DRIVE-AB consortium will dedicate considerable resources to this collaboration and to the final dissemination of information to policymakers and the wider public.Overall, we are confident that the work of the DRIVE-AB consortium will have an immense impact. This is an unprecedented gathering of experts and stakeholders, led by renowned experts in various fields of medical, public health and economic sciences, to solve