Epigenetic mechanisms, i.e. the control gene of expression without changing DNA sequence, include DNA methylation, histone post-translational modifications (PTMs) and microRNAs (miRNAs). Aberrant epigenetic modifications are associated with several pathological conditions, including brain diseases, resulting from environmental causes, ageing or genetic factors. The role of histone PTMs, including acetylation, phosphorylation, methylation and ubiquitylation, has been demonstrated in learning and memory, both in physiological conditions and in neuropathologies. Abnormalities in these modifications or in the machinery that control them are associated with several neurodegenerative, neuro-developmental and psychiatric diseases. Therefore, these epigenetic marks are promising targets to address memory-related diseases and strong efforts are presently focused on pharmacological and genetic approaches to this field.