Epigenetic regulation is critical for the normal development and functioning of our brain. Dynamic DNA and histone methylation as well as their demethylation at specific gene loci play a fundamental role in learning, memory formation and behavioral plasticity. The epigenome of neurons allows a molecular explanation for long-term memories. MECP2 is the best-characterized methyl-binding transcription factor and is involved both in gene activation and repression in the central nervous system. MECP2 is highly expressed in the brain and an important component of neuronal chromatin. Mutations in the MECP2 gene are the basis of the autism spectrum disorder Rett syndrome. In addition, also histone acetylation levels in neurons contribute to the cell’s proper function. Accordingly, HDAC inhibitors offer an effective therapy of some neurodegenerative diseases.