This chapter presents a brief discussion on the potential for contamination of the Pantanal by pesticides and reviews the studies, which evaluated these substances in different matrices in the Pantanal and its surroundings. Agricultural activities occur mainly in the highlands around the floodplain and represent the main source of pesticides to the Pantanal. It is evident that they can be transported to the lowlands, but the pesticides were detected in low frequency and concentrations so far. There is no monitoring program, and a few studies regarding this contamination are limited in sampling frequency and spatial distribution as well as in analyzed substances that considered the large spectrum of pesticides used. Moreover, only water and sediment have been subject to analysis, and no biological indicators have been studied. Also, to the moment, no risk analysis has been carried out indicating the need for more studies in the region in order to prevent future damages to this important ecosystem.