Early cytogenetic studies in bladder cancer identify regions of chromosomal gain or loss that can be candidate loci for oncogenes and tumor suppressor genes. Oncogenes with potential prognostic significance identified in bladder cancer the RAS family, epidermal growth factor receptor, ERBB-2, MDM2, and cyclin D1. The TP53 gene has been the most thoroughly characterized tumor suppressor gene in bladder cancer, with correlation of TP53 alterations with type of carcinogenic exposure, tumor stage and grade, as well as prognosis. Studies evaluating alterations of the retinoblastoma pathway have identified the retinoblastoma gene, RB, p161NK4A/CDKN2, and E2F-1 as tumor suppressor genes with potential prognostic significance in patients with bladder cancer. Better understanding of the genetic mechanisms underlying bladder tumor development and progression will allow better prevention, diagnosis, and treatment strategies.