Wastewater is a significant environmental and public health concern which management is a constant challenge since antiquity. Wastewater research has increased exponentially over the last decades. This paper provides a global overview of the exponentially increasing wastewater research in order to identify current challenges and paradigm shifts. Besides households, hospitals and typical industries, other sources of wastewater appear due to emerging activities like hydraulic fracturing. While the composition of wastewater needs constant reassessment to identify contaminants of interest, the comprehensive chemical and toxicological analysis remains one of the main challenges in wastewater research. Moreover, recent changes in the public perception of wastewater has led to several paradigm shifts: i) water reuse considering wastewater as a water resource rather than a hazardous waste, ii) wastewater-based epidemiology considering wastewater as a source of information regarding the overall health of a population through the analysis of specific biomarkers, iii) circular economy through the implementation of treatment processes aiming at harvesting valuable components such as precious metals or producing valuable goods such as biofuel. However, wastewater research should also address social challenges such as the public acceptance of water reuse or the access to basic sanitation that is not available for nearly a third of the world population.