Agroecology offers a scientific and operational framework for redesigning animal production systems (APS) so that they better cope with the coming challenges. Grounded in the stimulation and valorization of natural processes to reduce inputs and pollutions in agroecosystems, it opens a challenging research agenda for the animal science community. In this paper, we identify key research issues that define this agenda. We first stress the need to assess animal robustness by measurable traits, to analyze trade-offs between production and adaptation traits at within-breed and between-breed level, and to better understand how group selection, epigenetics and animal learning shape performance. Second, we propose research on the nutritive value of alternative feed resources, including the environmental impacts of producing these resources and their associated non-provisioning services. Third, we look at how the design of APS based on agroecological principles valorizes interactions between system components and promotes biological diversity at multiple scales to increase system resilience. Addressing such challenges requires a collection of theories and models (concept–knowledge theory, viability theory, companion modeling, etc.). Acknowledging the ecology of contexts and analyzing the rationales behind traditional small-scale systems will increase our understanding of mechanisms contributing to the success or failure of agroecological practices and systems. Fourth, the large-scale development of agroecological products will require analysis of resistance to change among farmers and other actors in the food chain. Certifications and market-based incentives could be an important lever for the expansion of agroecological alternatives in APS. Finally, we question the suitability of current agriculture extension services and public funding mechanisms for scaling-up agroecological practices and systems.