Nucleolar dominance is an epigenetic phenomenon that occurs in genetic hybrids and describes the expression of 45S rRNA genes inherited from one progenitor due to the silencing of the other progenitor’s rRNA genes. Nucleolar dominance is a manifestation of rRNA gene dosage control, which also occurs in non-hybrids, regulating the number of active rRNA genes according to the cellular demand for ribosomes and protein synthesis. Ribosomal RNA gene silencing involves changes in DNA methylation and histone modifications, but the molecular basis for choosing which genes to silence remains unclear. Recent studies indicate a role for short interfering RNAs (siRNAs) or structured regulatory RNAs in rRNA gene silencing in plants or mammals, respectively, suggesting that RNA may impart specificity to the choice mechanism.