Genetically determined risk factors may considerably contribute to the development of neoplastic diseases, including neoplasm of urinary organs, e.g. bladder and prostate cancers. It is believed that they may result, among others, from the differences in the metabolism of environmental carcinogens and mechanisms of DNA repair. There is a clear evidence that the kind and rate of metabolism is genetically determined by polymorphic enzyme coding genes participating in the process of xenobiotic transformation. Genetic polymorphism has been confirmed for a number of enzymes involved in the reaction of oxidation or conjugation of exo- and endogenous xenobioties. Gene variability may alter the expression or enzymatic activity of coded enzymes. Therefore, the cancer risk assessment should also be based on individual differences in the ability to activate (phase I) or to detoxify (phase II) possible carcinogens. In the present study, the information on the significance of glutathione 5-transferase (GST) and N-acetyltransferase (NAT) gene families in protection of human health and incidence of various diseases is summarized. The role of hereditary polymorphisms of GST and NAT genes involved in the etiology of neoplasm of urinary organs is controversial. That is why, special attention has to be focused on the recent information on a possible role of GST and NAT polymorphisms in the predisposition to urinary bladder, prostate and urothelial transitional cell carcinoma.