Over the past decade emerging evidence has indicated that epigenetic factors control and regulate nuclear processes. The genes encoding ribosomal RNA (rRNA) represent an ideal model to study how epigenetics and chromatin can modulate gene expression. The reason for this is that in each cell, the rRNA genes exist in two distinct types of chromatin structure: an 'open' one corresponding to transcriptionally active genes and a 'closed' one representing the silent genes. Recent studies indicate that an epigenetic network mediates the transcriptional state of rDNA. Interplay of DNA methylation, histone modification and chromatin-remodeling activities establishes silencing at the rDNA locus in higher eukaryotes as well as at the underdominant genes in hybrid cells. The aim of this review is to summarize current knowledge about the active and silent states of rRNA genes and of nucleolar organizing regions and to analyze the mechanisms involved in the establishment and inheritance of rDNA silencing.