Water quality models are in great demand to complement studies about the status of estuarine waters. However, local models do not perform well when boundary conditions are not properly defined and when biogeochemical processes are not described with adequate detail. This chapter presents advanced modeling applications to perform water quality studies in Portuguese estuaries. Boundary conditions for hydrodynamics and biogeochemistry are provided by the Portuguese Coast Operational Model, downscaled by using nested domains with increasing resolution from the regional to the local scale. The nested models of the estuaries are described, and case studies are presented for specific estuaries to compute sediment transport (Tagus estuary), to calculate residence time of water (Mondego estuary), to forecast quality of bathing waters (Estoril Coast), and to quantify nutrient fluxes between estuaries and the open ocean (Ria de Aveiro). The level of detail used to represent biological processes in water quality models is also addressed, including the description of a case study about modeling of species vulnerable to water quality, such as Zostera noltii in Ria de Aveiro. The need for high level of detail to represent microbial loop and carbon cycle in estuaries is discussed with the application of a complex biological model to the Tagus estuary.