The paper presents a critical overview of the first 50 years in the evolution of the activated sludge process. Recognition of the role of aeration and microbial activity in the purification of sewage in the early studies established the basis for the accidental discovery of the process, which was immediately adapted into practice. The problems encountered during operation started a period of empirical expansion with many process modifications. As scientific support lagged behind practice, efforts were then directed towards exploring and understanding the fundamentals of the system related to substrate removal mechanisms, microbiology, process kinetics and stoichiometry, nitrogen transformations and, then, translating accumulated information into design. Extensive research generated remarkable findings which should be regarded as major milestones for future progress in many areas such as fractionation of substrate and biomass, particle size distribution, and substrate storage. A rational foundation of the activated sludge process for the removal of organic carbon could then be established based on mass balance. This approach also defined essential parameters that could relate microbial reactions involved with plant design and operation. Scientific ideas and discoveries have also enabled conceptual development of many emerging technologies such as the sequencing batch reactor, enhanced biological phosphorus removal, the oxic-settling anaerobic process, and the super-fast membrane bioreactor.