The theoretical and methodological aspects of using the methods for characteristics of ecological well-being (EW) of the fluvial systems are considered. The problems of development of multi-criteria classifications of EW, stages and results of assessment research are discussed. Evaluation of EW can be performed on the basis of biocentrism or anthropocentric approach that takes into account the planning of rivers use for various purposes with special attention to conservation of environment. The assessment scales were developed with considering of each evaluation component and indicator approach. It was concluded that EW is an example of system emergent property that combines its ability to produce organic substances, to maintain high quality of the habitat, high biodiversity, resistance to changes of natural conditions and anthropogenic impacts. This research is focused on the development of models for quantitative integral assessment of fluvial systems state, their systemic properties that are characterized by the necessity of new functional units (integral and summarizing indicators) that reflect the system integrity. The development of integral indicators of EW is discussed on hypothetical examples of the “river-drainage area” systems and on the base of assessment of EW of real natural object (Msta River) and its drainage area.