Many countries have implemented policies to reduce the use of chemical inputs in agriculture. However, these policies face many obstacles that limit their effectiveness. The purpose of this paper is to review the main challenges associated with reducing chemical inputs in agriculture and to propose potential solutions. Our analysis, based on a literature review linking agronomy and economics, shows that several agronomic options have proven effective in reducing chemical inputs or mitigating their negative impacts. We argue that the organization of the agri-food system itself is a major barrier to their implementation. Involving all stakeholders, from the chemical input industry to consumers, and designing appropriate policy frameworks are key to address this issue. We recommend combining different policy instruments, such as standards, taxes and subsidies, in a simplified and coherent way to increase effectiveness and ensure better coordination in the adoption of sustainable practices.