This article illustrates the criteria that were applied to draw the plan with the aim of assessing the trends of several substances in sediment and biota of the Lagoon of Venice, taking into account the recommendations of Directive 2000/60/EC and the daughter Directives. For this purpose, contaminant concentrations coming from a survey conducted in 2005 were compared with the Italian EQS. Results allowed for the evaluation of spatial and temporal trends of several contaminants in sediments and mollusks of the Lagoon of Venice. They allowed us to focus on which compounds need further monitoring and, most of all, which pollutants require measures to reduce inputs.