Epigenetic modiﬁcations have been causally linked to cancer development and progression, and are potentially reversible by drug treatments. The N-terminal tails of histones contain amino acid residues modiﬁable by post-translational modifications such as acetylation. Given that HDAC inhibitors induce cancer cell differentiation and death, an increasing number of these compounds has been synthesized in the last ten years. Many HDAC inhibitors are in clinical trials for the treatment of cancer. Two of them, the hydroxamic acid (SAHA) and Romidepsin (FK 228), are approved in the second line treatment of refractory, persistent or relapsed Cutaneous T Cell Lymphoma (CTCL). The growing evidence of the potential benefits of an anti-cancer treatment based on the use of HDAC inhibitors have led to a large number of patent applications all over the world. The aim of this review is to give an overview of the basic current knowledge and molecular mechanisms of HDAC inhibitors and their clinical trials as well as to focus on the recent patent applications existing in the field of HDAC inhibitors and cancer treatment between 2008 and 2010 in USA.