UDP-glucuronosyltransferases (UGTs) represent major phase II drug metabolizing enzymes. They are part of a rapidly growing, sequence similarly based superfamily of UDP-glycosyltransferases, including a number of enzymes, which presumably are functionally unrelated to UGTs. The present commentary discusses evolutionary aspects of the large glycosyltransferase superfamily emphasizing functionally related members which share roles in detoxication and elimination of endo- and xenobiotics. The discussion starts with the two human UGT families and polymorphism frequencies in different populations. These families probably evolved in vertebrates as a result of the struggle against toxic phytoalexins at the hepatogastrointestinal barrier. Co-regulation of some UGTs with other drug metabolizing enzymes may also have evolved in the course of 'animal-plant warfare'. Related UDP-glucosyltransferases evolved in insects. Even in plants and bacteria UDP-glucosyltransferases have been characterized which may be functionally related.