Reversal of tumorigenic epigenetic alterations is an exciting strategy for anticancer drug development. Pharmacologic inhibition of histone deacetylases (HDACs) induces differentiation, proliferation arrest and apoptosis of cancer cells. In addition to their effects on histones, HDAC inhibitors increase the acetylation level of several non-histone proteins, such as transcription factors, cytoskeletal proteins and molecular chaperones, which are crucial in tumorigenesis. Most importantly, the therapeutic potential of HDAC inhibitors goes well beyond carcinogenesis and may include neurodegenerative and inflammatory disorders. This editorial discusses the implication of HDACs in carcinogenesis, the molecular basis of the selectivity of HDAC inhibitors and their possible therapeutic role in non-malignant pathologic conditions.