Regulation of gene expression occurs at different levels, from DNA to protein, and through various mechanisms. One of them is modification of the chromatin structure, which is involved in the definition of transcriptional active and inactive regions of the chromosomes. These phenomena are associated with reversible chemical modifications of the genetic material rather than with variability within the DNA sequences inherited by the individual and are therefore called 'epigenetic' modifications. Ablation of the molecular players responsible for epigenetic modifications often gives rise to neurological and behavioral phenotypes in humans and in mouse models, suggesting a relevant function for chromatin remodeling in central nervous system function, particularly in the adaptive response of the brain to stimuli. We will discuss several human disorders that are due to altered epigenetic mechanisms, with special focus on Rett syndrome.