Mental retardation (MR) is a highly diverse group of cognitive disorders. Gene defects account for about half of all patients and mutations causative for impaired cognition have been identified in more than 400 genes. While there are numerous genetic defects underlying MR, a more limited number of pathways is emerging whose disruption appears to be shared by groups of MR genes. One of these common pathways is composed of MR genes that encode regulators of chromatin structure and of chromatin-mediated transcription regulation. Already more than 20 "epigenetic MR genes" have been identified and this number is likely to increase in the coming years when deep sequencing of exomes and genomes will become commonplace. Prominent examples of epigenetic MR genes include the methyl CpG-binding protein MECP2 and the CREB binding protein, CBP. Interestingly, several epigenetic MR proteins have been found to interact directly with one another or act together in complexes that regulate the local chromatin structure at target genes. Thus, it appears that the functions of individual epigenetic MR proteins converge onto similar biological processes that are crucial to neuronal processes. The next challenge will be to gain more insight into patterns of altered DNA methylation and histone modifications that are caused by epigenetic gene mutations and how these will disrupt the brain-specific expression of target genes. Such research may reveal that a wide variety of mutations in the genetic code result in a more limited number of disruptions to the epigenetic code. If so, this will provide a rationale for therapeutic strategies.