The Phase II enzymes of xenobiotic metabolism are characterized by a high level of substrate diversity and genetic polymorphism. Genetic polymorphism of the Phase II enzymes can be of substantial clinical significance as some variants have differences in substrate specificity, stability and levels of expression. Variation in these factors can give rise to abnormal drug metabolism and susceptibility to carcinogens and toxins. A new approach to the discovery of additional members of Phase II enzyme families and the identification of polymorphic variants using searches of the EST databases has been investigated. The examples provided demonstrate that relatively simple search strategies can be highly productive.