Alterations in chromatin structure by histone post-translational modifications appear to play a central role in the regulation of gene transcription. Histone modifications consist of methylation, acetylation, phosphorylation and ubiquityination. Among them histone acetylation is of critical importance. The level of histone acetylation depends on the activity of two families of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs, which is frequently part of multisubunit coactivator complexes, lead to the relaxation of chromatin structure and transcriptional activation, while HDACs tend to associate with multisubunit corepressor complexes, resulting in chromatin condensation and transcriptional repression of specific target genes. Chromosomal translocations are often associated with acute leukemias, and a significant number of translocations involve genes encoding HATs and HDACs. On the other hand, some histone acetylation-modifying enzymes have been located within chromosomal regions that are particularly prone to chromosomal breaks. The recent achievements in studies aimed at elucidating the biological roles of histone acetylation modifying enzymes and their potential impacts on the molecular changes involved in the development of cancers are reviewed.