In this paper, the performance of the full-scale RO process with highly permeable membranes and the governing mechanisms were carefully studied. It was found that the performance of a full-scale RO process could be controlled by two possible mechanisms, namely mass transfer rate and thermodynamic limitations. Under relatively low driving pressure, it was controlled by mass transfer rate (water flux) of the membrane. However, with the highly permeable membrane, it is possible that the performance is limited by the thermodynamic limitation, in which the osmotic pressure becomes equal to the driving pressure inside of the membrane channel. A process controlled by thermodynamic limitation is an extremely case of the hydraulic imbalance problem. When it occurs, it means part of the membranes in the processes do not contribute to permeate production. More complicated are situations in the intermediate pressure range, in which both mechanisms contribute to, but none of them can dominate, the performance of the process. Some innovative concepts and theories on the performance of the full-scale RO processes were developed. These concepts and theories may provide better qualitative explanations for the behaviors often observed in the full-scale RO processes. A better quantitative simulations or predictions of the performance of the process were developed upon these concepts and theories. Experiments were carried out on a pilot membrane process of 6 m membrane channel to imitate the performance of the full-scale RO under various conditions. The experimental performance data were compared with theoretical simulations and excellent agreement was obtained. Another focus of this current study was on characterization and modeling of membrane fouling in the full-scale RO process. Colloidal fouling experiments were conducted to study the fouling potential of feed water and a new fouling indicator was proposed. The indicator can be directly used in the mathematical model to simulate fouling development in the full-scale RO processes. Model simulations showed that under certain condition (thermodynamic restriction), the recovery or average permeate flux of a full-scale RO process would maintain a constant value even membrane fouling was taking place. Experimental verification of the simulation results is currently under way. With the new developments and findings in this area, methods or protocols for optimization of full-scale processes of the highly permeable RO membranes were suggested.