Different computer-based simulation models, able to predict the performance of Reverse ElectroDialysis (RED) systems, are currently used to investigate the potentials of alternative designs, to orient experimental activities and to design/optimize prototypes. The simulation approach described here combines a one-dimensional modelling of a RED stack with a fully three-dimensional finite volume modelling of the electrolyte channels, either planar or equipped with different spacers or profiled membranes. An advanced three-dimensional code was used to provide correlations for the friction coefficient (based on 3-D solutions of the continuity and Navier-Stokes equations) and the Sherwood numbers (based on 3-D solutions of a scalar transport equation), as well as to test simple models for the Ohmic resistances (based on 3-D solutions of a Laplace equation for the electrical potential). These results were integrated with empirical correlations for the transport properties of electrolytes and membranes, and were used as the input for the higher scale model. The overall model was validated by comparison with experimental data obtained in laboratory-scale RED stacks under controlled conditions. This combined approach constitutes a fully predictive, potentially very accurate, and still extremely fast-running, tool for the approximate simulation of all the main variables, suitable for performance prediction and optimization studies.