The physical degradation of large regulated rivers in Europe and North America and the need for rehabilitation have become issues since the 1980s. Over the past years we have greatly increased our understanding of the ecological functioning of natural rivers, evaluated the ecological impacts of river regulation, and established various approaches for river rehabilitation and restoration. Complete restoration of large rivers may be a utopian idea because of the manifold functions they serve. It is not surprising, therefore, that rehabilitation attempts so far have only recovered stretches or certain features of rivers. The steps to he taken now are to share our expertise on river functioning, river management and rehabilitation, and to put this expertise into practice. This paper gives an overview of recent progress in Europe and North America structured along the following main questions: ○ Where are we heading, i.e. what are our references and how can we translate them into realizable end-points ○ What is our experience with past attempts of rehabilitation, and how can we best assess our past and future achievements? ○ How should we integrate rehabilitation into future river management to efficiently achieve our goals, i.e. where are the joint opportunities and opposing interests with other functions? ○ How do we optimize and prioritize our efforts to maximize ecological outcome, and in which form should those benefits be demonstrated? Following this analysis, we address management needs and make recommendations for a future research agenda on rehabilitation of large regulated rivers. Our goal is to incorporate a general understanding of large river functioning into the practice of river rehabilitation by: (a) defining tangible and attainable endpoints deduced from ecologically intact or pristine references either derived from reconstruction of historic conditions or from spatial analogues; (b) developing prognostic tools to link abiotic processes and patterns and biotic response at the appropriate spatial and temporal scales; and (c) optimizing rehabilitation within the multitude of functions large rivers fulfil and considering the heavily modified condition of most regulated large rivers. To achieve success in rehabilitation projects, all stakeholders should make better use of existing knowledge when they plan, execute and evaluate river rehabilitation. Well-documented pilot studies should be exploited since they give room for more adventurous rehabilitation not only along the same river but also elsewhere.