Bladder cancer incidence increases with age, presumably reflecting a cumulative exposure to carcinogens and ever-increasing life expectancy. While aberrant protein expression due to DNA mutations is an essential step during oncogenesis, one recent interest has been the role of epigenetic changes in regulating bladder tumor development. Because aberrant histone acetylation has been linked to malignant diseases in several cases, histone deacetylase inhibitors have great potential as new anticancer drugs owing to their ability to modulate transcription and induce differentiation and apoptosis. We herein review the current knowledge on epigenetic issues in bladder cancer, particularly regarding histone acetylation, and discuss its implications for understanding the molecular basis and treatment of this disease.