This work is the first step of a research project on pesticide risk assessment for a coastal lagoon ecosystem (Orbetello lagoon, central Italy). Pesticide exposure was evaluated by means of predictive and experimental approaches. Predicted environmental concentrations (PECs) for water and sediments were estimated using fugacity-based multimedia models. Pesticide loads were quantified through a study of the use to which agricultural land was put in the study area. Multimedia fate models were used to predict the environmental concentration of 29 active ingredients (mainly insecticides and herbicides) selected among the most widely used within the catchment basin. Worst-case environmental scenarios were developed for the application of these models, in agreement with the precautionary principle. Experimental monitoring was performed on 10 selected chemicals. To assess the value and limitations of predictive and experimental approaches, calculated PECs and monitoring results were compared and discussed. Combined modeling and monitoring approaches have been found to be the best way to date to assess proper exposure.