The paper summarizes the development in the understanding and practical application of the activated sludge process over the last 50 years. Since its invention, the activated sludge process has been a big challenge to design engineers. Traditionally, the technology was covered by sanitary engineers. However, with the development in the understanding of activated sludge process principles, further progress was not possible without knowledge of reaction kinetics and reactor theory. The shift from BOD removal only to combined removal of organic pollution, nitrogen and phosphorus required a chemical engineering approach with outputs of activated sludge microbiology and microbial ecology. Molecular biology enabled more accurate identification of important activated sludge microorganisms. The development in activated sludge process also required more efficient activated sludge separation and thickening. The paper describes the development from secondary clarifiers to membrane separation. Increasing water stress around the globe has also changed the main wastewater paradigm from wastewater treatment and safe discharge to safe reuse.