The ability to sustain antibiotic efficacy is directly affected by incentive models aiming to stimulate antibiotic research and development. This paper analyzes the extent to which the models proposed by the Innovative Medicine Initiative-funded research project DRIVE-AB can be expected to support sustainable use, drawing on basic economic theory and the incentives that derive from it. It then discusses the use of minimal safeguards that will be needed to support sustainable use where industry incentives have not been re-aligned with those of public health.