This paper introduces a novel concept for a hybrid desalination system that combines reverse electrodialysis (RED) and reverse osmosis (RO) processes. In this hybrid process the RED unit harvests the energy in the form of electricity from the salinity gradient between a highly concentrated solution (e.g., seawater or concentrated brine) and a low salinity solution (e.g., biologically treated secondary effluent or impaired water). The RED-treated high salinity solution has a lower salt concentration and serves as the feed solution for the RO unit to reduce the pump work. The concentrated RO brine provides the RED unit a better high salinity source for the energy recovery compared to seawater. In addition, the concentration of the discharged brine can be controlled by the RED unit for improving the water recovery and minimizing the impact on the environment. Different configurations of the hybrid RED–RO processes are presented for a comparative study on the basis of mathematical modeling. Specifically, various operating conditions for the RED unit are investigated for better adaptation to the hybrid system. The variations of the total specific energy consumption and the discharge brine concentration for various hybrid modes are simulated to verify the conceptual designs. The modeling results indicate that the RED–RO hybrid processes could substantially reduce the specific energy consumption and provide a better control of the discharge brine concentration in comparison to conventional seawater desalination RO processes.