New modeling approaches that include the use of GIS are under development in order to allow a more realistic assessment of environmental contamination by pesticides. This paper reports a regional GIS-based risk assessment using a software tool able to simulate complex and real crop rotations at the regional scale. A single pesticide leaching assessment has been done. The mean annual pesticide concentration in leachate has been analyzed using both stochastic and deterministic approaches. The outputs of these simulations were mapped over the sampling locations of the regional pesticide monitoring program, demonstrating that GIS-based risk assessment can be used to establish new monitoring programs. A multiple pesticide leaching assessment for analyzing the risk related to pest control strategies in six different maize-based rotations has been carried out. Additive toxic units approach has been used. Crop rotation allows to mediate the risk related to pesticide use because forces the use of different compounds with different fate and toxicology properties.