Genomes of higher eukaryotes contain abundant non-coding repeated sequences whose overall biological impact is unclear. They comprise two categories. The first consists of retrotransposon-derived elements. These are three major families of retroelements (LINEs, SINEs and LTRs). SINEs are clustered in gene-rich regions and are found in promoters of genes while LINEs are concentrated in gene-poor regions and are depleted from promoters. The second class consists of non-coding tandem repeats (satellite DNAs and TTAGGG arrays), which are associated with mammalian centromeres, heterochromatin and telomeres. Terminal TTAGGG arrays are involved in telomere capping and satellite DNAs are located in heterochromatin, which is implicated in transcription silencing by gene repositioning (relocalization). It is unknown whether interstitial TTAGGG sequences, which are present in many vertebrates, have a function. Here, evidence will be presented that retroelements and TTAGGG arrays are involved in regulation of gene expression. Retroelements can provide binding sites for transcription factors and protect promoter CpG islands from repressive chromatin modifications, and may be also involved in nuclear compartmentalization of transcriptionally active and inactive domains. Interstitial telomere-like sequences can form dynamically maintained three-dimensional nuclear networks of transcriptionally inactive domains, which may be involved in transcription silencing like classic heterochromatin. BioEssays 30:338–348, 2008. © 2008 Wiley Periodicals, Inc.