Abstract The presence of emerging contaminants (ECs) in the environment has been consistently recognized as a worldwide concern. ECs may be defined as chemicals or materials found in the environment at trace concentrations with potential, perceived, or real risk to the “One Health” trilogy (environment, human, and animal health). The main concern regarding pharmaceuticals and in particular antibiotics is the widespread dissemination of antimicrobial resistance. Nevertheless, non-antimicrobials also interact with microorganisms in both bulk phase and in biofilms. In fact, drugs not developed for antimicrobial chemotherapy can exert an antimicrobial action and, therefore, a selective pressure on microorganisms. This review aims to provide answers to questions typically ignored in epidemiological and environmental monitoring studies with a focus on water systems, particularly drinking water (DW): Do ECs exposure changes the behavior of environmental microorganisms? May non-antibiotic ECs affect tolerance to antimicrobials? Do ECs interfere with biofilm function? Are ECs-induced changes in microbial behavior of public health concern? Nowadays, the answers to these questions are still very limited. However, this study demonstrates that some ECs have significant effects in microbial behavior. The most studied ECs are pharmaceuticals, particularly antibiotics, carbamazepine and diclofenac. The pressure caused by antibiotic and other antimicrobial agents on the acquisition and spread of antibiotic resistance seems to be unquestionable. However, regarding the effects of ECs on the development and behavior of biofilms, the conclusions of different studies are still controversial. The dissimilar findings propose that standardized tests are needed for an accurate assessment on the effects of ECs in the microbiome of water systems. The variability of experimental conditions, combined with the presence of mixtures of ECs as well as the lack of information about the effects of non-pharmaceutical ECs constitute the main challenge to be overcome in order to improve ECs prioritization.