Since the early 1920’s, pharmaceuticals, including antibiotics, have been massively produced and consumed for the benefit of both human and animal health. Pharmaceuticals residues have then reached the aquatic environment through diffuse and point (wastewater) sources. Among the pharmaceutical residues, the ubiquitous presence of antibiotics could exert a selective pressure on microbial communities leading to the acquisition and dissemination of antibiotic resistance in the environment. We present here the synthesis of recent research projects (e.g. PANDORE, Antibio-tools, Antibiotox, PharmaTox...) investigating the dissemination of pharmaceuticals, including antibiotics, in the different aquatic compartments (surface water, periphyton, sediment) and its impact on periphyton and sediment microbial communities. These projects mainly focused on antibiotic resistance genes (ARG), community tolerance to pharmaceuticals (PICT) and antibiotic biodegradation capacity by combining field studies on different lake and lotic ecosystem (e.g. rivers Arve, Tillet and Le Clain; lake Geneva) and experimental approaches in microcosms. Our results highlight the ubiquitous presence of pharmaceuticals in the studied ecosystems and the specific distribution of pharmaceuticals in the different investigated compartments. The field surveys generated an important antibiotic resistance database including relative abundance of ARG and genetic mobile elements as well as functional measurements of microbial tolerance (PICT approach) to selected pharmaceuticals and biodegradation potential of sulfonamide antibiotics. Antibiotic resistance was found to be positively correlated with the presence of wastewater treatment plant effluents, but we confirm that the links between exposure levels, i.e. antibiotics concentrations, and antibiotic resistance must be considered in all ecosystem complexity. Further analyses are currently on-going to better take into account potential confounding factors. These research projects generated advances in our knowledge on pharmaceuticals and antibiotic resistance dissemination within the aquatic environment but also reveal the current challenges to better understand the drivers of antibiotic resistance in such complex environments.