Post-translational modifications, such as acetylation or phosphorylation, play a crucial role in the regulation of gene transcription in eukaryotes. Different subtypes of histone acetyl transferases (HATs) catalyze the acetylation of histones on specific lysine residues. A potential role of HATs in the pathology of cancer, asthma, COPD and viral infection has been described. This indicates that specific HAT inhibitors are potential tools for pharmacological research and might find therapeutic applications. This review focuses on the role of the HATs p300, CBP, PCAF and GCN5 in different diseases and the development of small-molecule inhibitors of these enzymes as potential drugs.