Histone deacetylase inhibitors (HDACIs) represent one of the most promising, recently developed classes of anticancer agents
already approved by the U.S. FDA. The effectiveness of these new drugs has currently being explored in a variety of cancer cell lines, in
vitro, animal models, in vivo, as well as in clinical trials. Malignant mesothelioma (MM) is a rare aggressive malignancy with a median
overall survival of 12 months when the current chemotherapy regimen, cisplatin-pemetrexed, is applied. This disappointing overall
survival has encouraged the experimental use of novel pharmaceutical agents, including HDACIs. In this aspect, the present review is
aimed to summarize the existing data regarding the potential utility of HDACIs as therapeutic targets for the treatment of MM. Taking
into consideration the research investigations so far, both in vitro and in vivo studies have documented encouraging results. Promising
results are also being expected by ongoing clinical trials that concern combination of chemotherapy with HDACIs against MM.