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This article aims to provide a review of major challenges and research needs for the diffusion of conservation agriculture (CA) and the improvement of crop–soil–water conditions in Southern Europe and Northern Africa. A multidisciplinary study and a participatory approach are at the basis of an international project of research and innovation action, “Research-based participatory approaches for adopting conservation agriculture in the Mediterranean Area-CAMA”. It aims to understand the reasons and the research needs that limit a large CA diffusion in the Mediterranean countries. CAMA aims to provide significant advances to CA through multidisciplinary research at the field and farm scales (with main emphasis on smallholder), encompassing a socio-economic analysis of the reasons that obstacle the CA diffusion, legume crop improvement as a component of improved CA cropping systems, and a network of long-term experiments on CA and soil characteristic modification. Its results will be available to scientific and farming communities.