Most of the human genome is compacted into heterochromatin, a form that encompasses multiple forms of inactive chromatin structure. Transcriptional silencing mechanisms in budding and fission yeasts have provided genetically tractable models for understanding heritably repressed chromatin. These silent domains are typically found in regions of repetitive DNA, that is, either adjacent to centromeres or telomeres or within the tandemly repeated ribosomal DNA array. Here we address the mechanisms of centromeric, telomeric and locus-specific gene silencing, comparing simple and complex animals with yeast. Some aspects are universally shared, such as histone-tail modifications, while others are unique to either centromeres or telomeres. These may reflect roles for heterochromatin in other chromosomal functions, like kinetochore attachment and DNA ends protection.