Bladder cancer is an excellent system in which to study molecular events in the initiation and progression of a malignancy. This review focuses on chemical carcinogenesis, cytogenetics, tumor suppressor genes, oncogenes, growth factors, and metastasis in bladder cancer. Where possible, the molecular information will be correlated with well described epidemiologic, pathologic, and clinical risk factors. Critical appraisal of some of the most recently described genetic changes is provided.