Epigenetic mechanisms are increasingly recognized as a major factor contributing 
to pathogenesis of cancer including glioblastoma, the most common and most 
malignant primary brain tumour in adults. Enzymatic modifications of histone 
proteins regulating gene expression are being exploited for therapeutic drug 
targeting. Over the last decade, numerous studies have shown promising results 
with histone deacetylase (HDAC) inhibitors in various malignancies. This article 
provides a brief overview of mechanism of anti-cancer effect and pharmacology of 
HDAC inhibitors and summarizes results from pre-clinical and clinical studies in 
glioblastoma. It analyses experience with HDAC inhibitors as single agents as 
well as in combination with targeted agents, cytotoxic chemotherapy and 
radiotherapy. Hallmark features of glioblastoma, such as uncontrolled cellular 
proliferation, invasion, angiogenesis and resistance to apoptosis, have been 
shown to be targeted by HDAC inhibitors in experiments with glioblastoma cell 
lines. Vorinostat is the most advanced HDAC inhibitor that entered clinical 
trials in glioblastoma, showing activity in recurrent disease. Multiple phase II 
trials with vorinostat in combination with targeted agents, temozolomide and 
radiotherapy are currently recruiting. While the results from pre-clinical 
studies are encouraging, early clinical trials showed only modest benefit and 
the value of HDAC inhibitors for clinical practice will need to be confirmed in 
larger prospective trials. Further research in epigenetic mechanisms driving 
glioblastoma pathogenesis and identification of molecular subtypes of 
glioblastoma is needed. This will hopefully lead to better selection of patients 
who will benefit from treatment with HDAC inhibitors.