Recent studies have provided the first clues as to the molecular mechanisms responsible for bladder carcinogenesis. Cytogenetic and molecular studies have demonstrated nonrandom changes of chromosomes 1, 5, 7, 9, 11, and 17. The finding of monosomy of chromosome 9 in early noninvasive lesions has initiated a search for a bladder-specific gene responsible for bladder oncogenesis. Activation of ras and erbB oncogenes has been reported, although the role that these changes play in bladder cancer is not yet understood. Inactivation of two well-characterized tumor suppressor genes, p53 and Rb, also appears to be important in the pathogenesis of bladder cancer, and evidence suggests that inactivation of p53 correlates with the acquisition by bladder cancer cells of the invasive phenotype. Although the picture is far from complete, it is clear that for the first time an understanding of the molecular events responsible for bladder cancer is possible, and that this information will have clinical impact on patients in the near future.