Establishment and inheritance of heterochromatic states is critical in maintaining genome integrity and gene expression state. The elucidation of the mechanisms implicated in these processes is fundamental to understand the control of epigenetic regulation of the genome. Recently, the nucleolus emerged as an important component of the nuclear architecture. Although the nucleolus is the most active site of cellular transcription, it is also an attractive compartment for nuclear heterochromatic regions, such as pericentric repeats, inactive X chromosome and regions with low gene density significantly enriched in repressed genes. The coexistence of euchromatic and heterochromatic rRNA genes in each cell reflects these two opposite functions of the nucleolus. An epigenetic network that is controlled by NoRC complex establishes and maintains rDNA heterochromatin. It is here discussed how heterochromatic rRNA genes and the associated epigenetic regulatory activities might mediate formation and inheritance of nuclear heterochromatic regions. Finally, we propose that the analysis of the components of heterochromatic rRNA genes will be not only relevant to understand the general composition of heterochromatin but has the potential to provide important and novel insights of how nuclear heterochromatic structures are established and inherited.