Leukemia is a type of cancer caused by the acquisition of gene mutations that bestow deregulated proliferation, impaired differentiation. There is continuing interest to recognize the signaling pathways and genes that play a crucial function in carcinogenesis and the development of resistance to antitumor drugs. The histone deacetylases (HDACs) has been found to interact with many partners through complex molecular mechanism leading to the regulation of gene expression, they have obtained the interest of a large number of researchers. Several HDAC inhibitors (HDACis) have been confirmed to proficiently protect against the growth of tumor cells in vitro as well as in vivo. Thus it is expected that some of the HDACi could be potential effective anti-leukemic drugs. In this book, we have summarized the current status of different classes of HDACs, epigenesis, apoptosis and role of HDAC inhibitors in therapeutics for the treatment of different types of leukemia.