Recently, we have discovered, dubbed PTE-Like Lactonases (PLL) and ascribed to the amidohydrolase superfamily. a new family of microbial lactonases with promiscuous phosphotriesterase activity. Among members of this family are enzymes found in the Archaea: Sulfolobus solfataricus and Sulfolobus acidocaldarius, which show high thermophilicity and thermal resistance. From a biotechnological point of view enzymes endowed with phosphotriesterase activity are attractive objects of study because are capable to hydrolyse the organophosphate phosphotriesters (OPs), a class of worldwide used synthetic compounds employed both as insecticides and chemical warfare agents. From the viewpoint of basic research, studies of catalytic promiscuity offer clues to understand the natural evolution of enzymes and to translate this knowledge into in vitro adaptation of catalysts to specific human needs. Thermostable enzymes able to hydrolyse natural lactones and promiscuously OPs are currently considered good candidates for the set-up of efficient anti-microbial and detoxification tools. We will report on our attempts to follow these two paths.