Aim and subject: Antibiotic resistance is a serious threat to public health in Europe leading to increasing health-care costs and deaths. Combating antibiotic resistance requires an understanding of the ecology of antibiotic-resistance genes (ARGs), their selection, and their spread in the environment. Although antibiotic resistance has involved research in clinically relevant human pathogens, environmental reservoirs and the contribution of ARGs in clinical settings have only been considered recently. Results: In this article we discuss the links between human activities and the natural ecosystem that might influence the evolution and spread of ARGs with a special focus on wastewater treatment plants (WWTPs). Moreover, traditional and novel techniques aiming toward a better understanding of this problem are elucidated. Conclusion: Routine monitoring programs are recommended to provide background data for mitigation activities in WWTPs based on the presence of ARGs, the abundance of antibiotics, as well as the presence of resistant bacteria in the environment.