This paper sets the stage for this Special Issue covering a set of papers, which try to provide a cross-scale evaluation of the trade-offs and synergies evident among aquaculture, water quality and environment in the empirical context of 8 different countries from Asia and Africa. Having discussed the livelihood and policy significance of the issue of cross-scale trade-offs and synergies, this paper provides an eclectic review of literature to show how this issue has been insufficiently treated in past studies. With a brief overview and synthesis of the papers included in this Issue, this paper also indicates how they overcome the analytical, methodological, and data challenges so as to provide a cross-scale evaluation of the trade-offs and synergies in different empirical settings. After illustrating how the new research insights can be integrated into the public debates and policy processes, this paper concludes with the identification of future research and policy needs.