The important role of histone deacetylase enzymes in regulating gene expression, cellular proliferation, and survival has made them attractive targets for the development of histone deacetylase inhibitors as anticancer drugs. Suberoylanilide hydroxamic acid (Vorinostat, Zolinza), a structural analogue of the prototypical Trichostatin A, was approved by the US Food and Drug Administration for the treatment of advanced cutaneous T-cell lymphoma in 2006. This was followed by approval of the cyclic peptide, depsipeptide (Romidepsin, Istodax) for the same disease in 2009. Currently numerous histone deacetylase inhibitors are undergoing preclinical and clinical trials for the treatment of hematological and solid malignancies. Most of these studies are focused on combinations of histone deacetylase inhibitors with other therapeutic modalities, particularly conventional chemotherapeutics and radiotherapy. The aim of this paper is to provide an overview of the classical histone deacetylase enzymes and histone deacetylase inhibitors with an emphasis on potential combination therapies.