Nowadays, one of the major challenges in the wastewater sector is the successful design and reliable operation of treatment processes, which guarantee high treatment efficiencies to comply with effluent quality criteria, while keeping the investment and operating cost as low as possible. Although conceptual design and process control of activated sludge plants are key to ensuring these goals, they are still based on general empirical guidelines and operators' experience, dominated often by rule of thumb. This review paper discusses the rationale behind the use of Computational Fluid Dynamics (CFD) to model aeration, facilitating enhancement of treatment efficiency and reduction of energy input. Several single- and multiphase approaches commonly used in CFD studies of aeration tank operation, are comprehensively described, whilst the shortcomings of the modelling assumptions imposed to evaluate mixing and mass transfer in AS tanks are identified and discussed. Examples and methods of coupling of CFD data with biokinetics, accounting for the actual flow field and its impact on the oxygen mass transfer and yield of the biological processes occurring in the aeration tanks, are also critically discussed. Finally, modelling issues, which remain unaddressed, (e.g. coupling of the AS tank with secondary clarifier and the use of population balance models to simulate bubbly flow or flocculation of the activated sludge), are also identified and discussed.