Abstract The quantum chemically based conductor-like screening model for realistic solvation COSMO-RS is a rather general method for predicting the chemical potentials – and thus the activity coefficients – of almost arbitrary molecules in almost any dense pure or mixed liquid. Originally it was developed for the prediction of partition coefficients and Henry’s law constants which are important in environmental and life science, almost all of them involving the aqueous phase. Partitioning between organic phases, as essential in many chemical engineering applications, was considered only in later stages. Therefore, the solvent water had and still has a great importance in the parameterization and validation of COSMO-RS with the result, that aqueous solvation in generally is well described. In this article, we review the performance of COSMO-RS for aqueous solvation, discuss some problems arising for this special fluid, i.e., water, and review some recent extension of COSMO-RS to p K a prediction, electrolyte systems, and aqueous interfaces.