Epigenetic regulators such as histone acetyltransferases (HATs) and histone deacetylases (HDACs) are known to play an important role in gene expression. Of these enzymes, HDACs have been shown to be commonly associated with many types of cancers and to affect cancer development. Consequently, HDACs have been considered as promising targets for cancer therapy. In addition, the inhibition of HDACs by histone deacetylase inhibitors (HDACIs) shifts the balance between the deacetylating activity of HDACs and the acetylating activity of HATs in the regulation of gene expression. Therefore, HDACIs are an exciting new addition in cancer therapies. Numerous HDACIs have been identified and some have recently been used in clinical trials for cancer treatment, although the mechanisms underlying the anticancer effects of HDACIs remain unclear. In this review, we examine the most recent developments in HDACIs and various aspects of HDAC-targeted cancer treatment.