A unified approach for the evaluation of alternative renewable-energy-powered desalination systems and their comparison on the basis of the economics of the associated investments is presented. The proposed method works out a preliminary plant design, evaluates the energy flows and calculates the water cost and the expected water selling price. The energy needs of the desalination processes and the energy production by the renewable energy technologies are estimated using simplified models. The size and type of the back-up power units (energy storage, grid connection or diesel generators) are identified. The expected water selling price is estimated, taking into account the water production cost and the investment profitability index. The computer-aided design tool that has been developed proposes technology combinations that guarantee the desalination energy needs and provides the means to compare the alternative options on the basis of economic indicators. Results on alternative RE-desalination combinations are presented in order to select the optimum solution for a specific case study. The effect of critical design parameters on the water selling price is analyzed for a wind-powered reverse osmosis plant.