Histone acetyltransferases (HATs) are critical in controlling H3 lysine acetylation and are tightly associated with cell cycle regulation, cell proliferation, and apoptosis. Histone acetylation also has impact on the regulation of chromatin structure and the recruitment of transcription factors to gene promoters. A disrupted equilibrium of histone acetylation is correlated with diseases ranging from cancers and inflammatory diseases to neurological disorders. The investigation of histone acetylation pattern leads to a better understanding of epigenetic regulation of gene activation, and helps to develop drugs targeting HAT. Although some HAT inhibitors have been developed, there still remains a large gap between the biological activity of inhibitors in in vitro studies and their potential use as therapeutic agents.