Hydropower is a vital renewable energy source but has substantial ecological impacts on rivers, lakes, and surrounding ecosystems. It alters hydrogeomorphology, disrupts connectivity, and changes water physicochemical properties such as temperature and dissolved gas concentrations. Historically, the environmental impact has been of less concern compared to energy production, and there is an urgent need to adapt hydropower production to reduce impacts on aquatic ecosystems. While various mitigation measures exist, a systematic understanding of their efficiency is lacking. Here, we extensively review both the environmental effects of hydropower and the scientific base for mitigation measures. We then list key abiotic and biological candidates for systematic monitoring before outlining a programmatic monitoring approach to evaluate the efficiency of mitigation measures. This programmatic monitoring approach involves monitoring packages based on specific mitigation measures. A set of abiotic parameters and biological indicators are monitored with standardized methods and monitoring designs over the long-term and at several sites, covering different river types and hydropower configurations. The proposed program serves to inform ongoing and future remedial measures, expand our mechanistic understanding of the ecological effects, facilitate knowledge transfer, and allow for more reductionist monitoring approaches outside of the program.