Since the first report of p53 as a non-histone target of a histone acetyltransferase (HAT), there has been a rapid proliferation in the description of new non-histone targets of HATs. Of these, transcription factors comprise the largest class of new targets. The substrates for HATs extend to cytoskeletal proteins, molecular chaperones and nuclear import factors. Deacetylation of these non-histone proteins by histone deacetylases (HDACs) opens yet another exciting new field of discovery in the role of the dynamic acetylation and deacetylation on cellular function. This review will focus on these non-histone targets of HATs and HDACs and the consequences of their modification.