In the mechanisms of carcinogenesis, it is becoming apparent that not only genetic abnormalities including DNA mutations, but also epigenetic abnormalities are heavily involved. Simultaneously, certain kinds of compounds indicated anti-tumor activity through their epigenetic effects. Typical drugs, which have the epigenetic effects, are histone deacetylase(HDAC) inhibitors. So far, two types of HDAC inhibitors, vorinostat and romidepsin, are approved by the Food Drug Administration for cutaneous T-cell lymphoma in the U. S. A. Not only these two compounds but also many HDAC inhibitors are under clinical trials in monotherapy and combination therapy. For a better outcome, it is very important to establish the appropriate biomarkers and appropriate combination based on mode-of-action for HDAC inhibitors, similar to other molecular-target antitumor drugs.