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This article is the result of work that was presented at the PharmaAQUA seminar (March 9–11, Annecy, France). It contributes toward knowledge on the pollution of inland aquatic ecosystems by pharmaceutical residues (PR) and antibiotic-resistant bacteria (ARB). Pollution of these ecosystems by PR occurs around the world. The main sources are effluent from wastewater treatment plants (WWTP) and the spreading of organic waste products of animal origin (manure and slurry). French rivers are no exception and contain PR in concentrations ranging from nanograms per liter to micrograms per liter, depending on the molecule. This chronic contamination generates risks and ecotoxicological effects to which microbial communities are potentially vulnerable. Their alteration can indirectly affect the biodiversity and functioning of ecosystems. The Pollution-Induced Community Tolerance (PICT) approach is a promising tool for diagnosing chemical pollution by PR. Aquatic environments are polluted by antibiotic residues and other chemical contaminants which create favorable conditions for the formation of a reservoir of antibiotic resistance genes (ARG). Bacterial biofilms and sediments are trapping zones for ARB and ARG. Their study notably revealed an accumulation of ARB and ARG downstream of WWTPs. Urban and hospital effluents have specific signatures for ARG. The improvement of wastewater treatment by WWTPs, the reduction of discharges at source (through information, greater awareness, and changes in practices), and better monitoring of pharmaceutical production are all levers that are being studied to control this pollution. This requires multiple and coordinated efforts to be made at the intersection between human health, animal health, and water by all actors involved in the issue.