This chapter discusses the epigenetics of brain disorders. Epigenetic mechanisms play a pivotal role in higher-order brain functions under physiological and pathological conditions. A deeper understanding of these mechanisms is of utmost importance for the development of potential treatments against brain disorders involving aberrant epigenetic modifications. Promising results have already been obtained, in particular with the use of histone deacetylases HDAC inhibitors. However, most of these inhibitors are nonspecific, and more research is needed to better understand their mechanisms of action before any treatment can be safely administered. It is therefore important to not only identify more specific HDAC inhibitors, but also to determine which HDACs are involved in different disease states. In this direction, it was recently demonstrated that although HDAC1 and HDAC2 are structurally related class I HDACs that often form functional heterodimers, only HDAC2 is causally implicated in the negative regulation of memory formation and synaptic plasticity