Despite continuous developments in the field of MBR technology, membrane fouling together with the associated energy demand and related costs issues remain major challenges. The efficiency of the filtration process in an MBR is governed by the activated sludge filterability, which is still limitedly understood and is determined by the interactions between the biomass, the wastewater and the applied process conditions. The purpose of this thesis is to increase understanding of the factors impacting activated sludge filterability during full-scale membrane bioreactor (MBR) operation. The overall research goal was to determine conditions for enhanced and efficient operation of the MBR technology. The research work included both extended on-site measurements and operational data analysis. Filterability of the activated sludge was experimentally determined in full- and pilot-scale MBRs treating both municipal and industrial wastewater. Subsequently, the most influential parameters influencing activated sludge filterability were determined. In addition, the design, operational and performance data were collected from the selected full-scale MBR plants and analysed in respect to plant functioning, i.e., operation, energy efficiency and operational costs. Therefore, the research links activated sludge filterability assessment and full-scale MBR functioning, i.e., design options, operation, performance and energy efficiency. Overall, it can be concluded that good filterability of the activated sludge is indispensable for efficient and optimal operation of an MBR. Operation with poor sludge filterability will be associated with a cost penalty due to sub-optimal filtration conditions. Wastewater composition and temperature are important influencing parameters with respect to filterability. MBR plant layout and membrane configuration influence overall MBR functioning and should be chosen carefully. The energy efficiency of an MBR is driven by the hydraulic utilization of the membranes and can be improved by implementation of flow equalization, new aeration strategies and adjusting operational settings to the incoming flow.