Global aquatic biodiversity keeps declining rapidly, despite international efforts providing a variety of policies and legislations that identify goals for, and give directions to protecting the world's aquatic fauna and flora. With the H2020 project AQUACROSS, we have made an unprecedented effort to unify policy strategies, knowledge, and management concepts of freshwater, coastal, and marine ecosystems to support the achievement of the targets set by the EU Biodiversity Strategy to 2020. AQUACROSS has embraced the concept of ecosystembased management (EBM), which approaches environmental management from a social-ecological system perspective to protect biodiversity and to sustainably harvest ecosystem services. This special issue includes contributions resulting from AQUACROSS, which either tackle selected EBM challenges from a theoretical point of view or apply EBM in one of the selected case studies across Europe. In this article, we introduce relevant topics, address the most important lessons learnt, and suggest where research should go with aquatic EBM. We hope that this special issue will foster and facilitate the uptake of EBM in aquatic ecosystems and, therewith, provide the on-ground applications needed for evaluating EBM's utility to safeguard aquatic biodiversity.