Ecosystem fragmentation is a serious threat to biodiversity and one of the main challenges in ecosystem restoration. River continuity restoration (RCR) has often targeted diadromous fishes, a group of species supporting strong cultural and economic values and especially sensitive to river fragmentation. Yet it has frequently produced mixed results and diadromous fishes remain at very low levels of abundance. Against this background, this paper presents the main challenges for defining, evaluating and achieving effective RCR. We first identify challenges specific to disciplines. In ecology, there is a need to develop quantitative and mechanistic models to support decision making, accounting for both direct and indirect impacts of river obstacles and working at the river catchment scale. In a context of dwindling abundances and reduced market value, cultural services provided by diadromous fishes are becoming increasingly prominent. Methods for carrying out economic quantification of non-market values of diadromous fishes become ever more urgent. Given current challenges for rivers to meet all needs sustainably, conflicts arise over the legitimate use of water resources for human purposes. Concepts and methods from political science and geography are needed to develop understandings on how the political work of public authorities and stakeholders can influence the legitimacy of restoration projects. Finally, the most exciting challenge is to combine disciplinary outcomes to achieve a multidisciplinary approach to RCR. Accordingly, the co-construction of intermediary objects and diagrams of flows of knowledge among disciplines can be first steps towards new frameworks supporting restoration design and planning.