Initially characterized for its ability to hydrolyze organophosphorus (OP) compounds, Paraoxonase- 1 (PON1) has been reported to play an important role in modulating the toxicity of some of these agents, which are “in vitro” substrates for this enzyme. The PON1 polymorphism at position 192 confers different enzyme levels and catalytic activity in a substrate-dependent manner, which has been related to the differential sensitivity of individuals to the toxic effects of OPs, supporting a role for the enzyme as a susceptibility biomarker. Several epidemiologic studies have examined the involvement of PON1 in xenobiotic susceptibility in different scenarios, including occupational exposure to pesticides. The major results of our studies performed in plastic greenhouses workers from Southeast Spain are presented herein. Briefly, PON1 is not only an individual marker of susceptibility, but also a biological indicator of exposure to pesticides, since workers spraying these agents, mainly OPs, showed decreased enzyme levels. On the other hand, carriers of the PON1 192R allele had lower levels of erythrocyte cholinesterase, a lower risk of presenting pesticide-related symptomatology, and less risk of reporting a previous episode of pesticide poisoning. Regarding enzymes involved in oxidative stress, carriers of the PON1 R allele had higher glutathione reductase and lower catalase activities. Intriguingly, PON1 R allele was found to be an independent predictor of higher aspartate aminotransferase and lower amino-oxidase and creatine kinase activities in serum. These findings deserve further attention as they highlight the important role of individual biomarkers of susceptibility on pesticideinduced biochemical changes in target organs that may precede the appearance of clinical changes.