Identification of genetic alterations in bladder cancer is proceeding very rapidly. The most common genetic alteration identified to date in bladder cancer is loss of heterozygosity of chromosome 9, suggesting a possible tumor-suppressor gene on this chromosome. Because none of the Ta tumors showed loss of heterozygosity of 9p, it may be possible to speculate that inactivation of a gene located on 9q may be the earlier event. The genes p53 and pRb have been associated with disease progression and survival; what is more important is that this effect is more pronounced if both markers are altered. One may postulate from these results that the loss of the function of wild-type p53 allows cells with DNA damage to proceed through the cell cycle, replicating genetic errors. Similarly, loss of normal pRb disrupts regulation of cell cycle, and thus decreased pRb expression in bladder cancer correlates with increased mitotic index. It has been shown that adjuvant chemotherapy affects favorably only those patients with p53-altered tumors with regard to decreased risk of recurrence and increased survival. Thus, p53 may be useful not only in predicting the aggressive nature of the tumor, but also in identifying patients who will not benefit from chemotherapy. Significant tumor reduction and a high local control rate were clearly demonstrated by a combination of radiation and radiosensitizing agents. Although promising survival rates with intact bladders have been reported, only a selected group of patients with muscle-invasive disease may benefit from this approach. Further studies in molecular genetics surely will enable a more refined approach for selecting treatment modalities in bladder cancer.