Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail,chromatin conformation, protein-DNA interaction, and even transcription. HDACs arealso post-transcriptional modifiers that regulate the protein acetylation implicated inseveral pathophysiologic states. HDAC inhibitors have been highlighted as a novel categoryof anti-cancer drugs. To date, four HDAC inhibitors, Vorinostat, Romidepsin,Panobinostat, and Belinostat, have been approved by the United States Food and DrugAdministration. Principally, these HDAC inhibitors are used for hematologic cancersin clinic with less severe side effects. Clinical trials are continuously expanding to addressother types of cancer and also nonmalignant diseases. HDAC inhibition also resultsin beneficial outcomes in various types of neurodegenerative diseases, inflammationdisorders, and cardiovascular diseases. In this review, we will briefly discuss1) the roles of HDACs in the acquisition of a cancer’s phenotype and the generaloutcome of the HDAC inhibitors in cancer, 2) the functional relevance of HDACs in cardiovasculardiseases and the possible therapeutic implications of HDAC inhibitors incardiovascular disease.