The fragile X mental retardation 1 gene (FMR1)‐related disorder fragile X syndrome (FXS) is the most common heritable form of cognitive impairment and the second most common cause of comorbid autism.FXSusually results when a premutation trinucleotideCGGrepeat in the 5′ untranslated region of theFMR1gene (CGG55–200) expands over generations to a full mutation allele (CGG>200). This expansion is associated with silencing of theFMR1promoter via an epigenetic mechanism that involvesDNAmethylation of theCGGrepeat and the surrounding regulatory regions. Decrease inFMR1transcription is associated with loss of theFMR1protein that is needed for typical brain development. The past decade has seen major advances in our understanding of the genetic and epigenetic processes that underlieFXS. Here we review these advances and their implications for diagnosis and treatment for individuals who haveFMR1‐related disorders.What This Paper AddsImproved analysis of DNA methylation allows better epigenetic evaluation of the fragile X gene.New testing techniques have unmasked interindividual variation among children with fragile X syndrome.New testing methods have also detected additional cases of fragile X.