A unified mathematical model is developed to describe both brackish water (BW) and seawater (SW) reverse osmosis (RO) desalination processes. The model contains two dimensionless parameters: kappa, quantifying the effect of retentate pressure drop, and gamma, reflecting the membrane capacity demand ratio. A gamma vs. kappa map derived from data obtained from RO desalination plants worldwide is used to show that BWRO and SWRO are in completely different regions. The minimization of specific energy consumption (SEC) is formulated and solved as a nonlinear optimization problem using representative values of gamma and kappa in both BWRO and SWRO. Several computational case studies are carried out to demonstrate the differences in operating BWRO and SWRO. Discussions are made on the effect of fractional recovery, RO configurations (single-stage, two-stage, and two-stage with booster pump) as well as brine recirculation on SEC.