Introduction: Enhanced understanding of the pathogenesis of Myeloproliferative Neoplasms (MPN) has led to the rapid introduction of novel therapeutic agents into clinical practice. Knowledge of the genetic landscape (eg. JAK2, MPL and CALR as commonly mutated genes) is increasing and has been used to model novel, effective therapies. Histone Deacetylases (HDAC) are heavily involved in epigenetic modulation; their aberrant expression has been demonstrated, both in vitro and in vivo, in various MPN. A number of HDAC inhibitors (HDACi) have since been developed with the aim to reverse this epigenetic dysregulation. Areas covered: The role of HDACi in MPN is reviewed in detail in addition to an update on the currently available clinical trial information. It is of pivotal importance to understand how these agents fit into the current therapeutic strategy for management of MPN. Expert opinion: HDACi certainly have a role in the management of MPN but clarification on the dosing and scheduling is required. Moreover, whether these agents should be used sequentially to agents such as JAK inhibitors or in combination is an area of active investigation.