Résumé: In the Mediterranean Sea, socio-economic drivers may accelerate the process of exclusive economic zone (EEZ) declarations. Despite the challenges, the EEZ declarations may provide important opportunities for leveraging change to national policy towards the development of large-scale conservation of marine ecosystems and biodiversity in this zone. Using the Mediterranean Sea as a case study, we aim to highlight a set of best practices that will maximize the potential for the development of large-scale marine conservation initiatives. These include a range of approaches, such as using surrogates to fill the many biodiversity data gaps in the region, further the development of consistent and open access databases, and the utilization of technological developments to improve monitoring, research and surveillance of less accessible and under-explored marine areas. The integration of Mediterranean-wide and local conservation efforts, the facilitation of transboundary collaboration, and the establishment of regional funds for conservation will further enhance opportunities for marine conservation in this region.