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Bisphenol A (BPA) has been described as a estrogenic compound. However, it is used in the production of polycarbonate, epoxy resins and other plastics. Mixed microbial cultures, such as activated sludge, have been proposed as a feasible methodology to achieve the decontamination of wastewater containing BPA. In this book, the biodegradation of bisphenol A (BPA) using activated sludge not previously exposed to BPA (native activated sludge) was described. In addition, the acclimation process to BPA and the strategies of acclimation of the biomass to the xenobiotic compound were analyzed. The kinetics and stoichiometry of the biodegradation of BPA and its metabolic products were determined. Finally, the biodegradation of BPA in the presence of a biogenic substrate in semi-continuous activated sludge reactors was studied.