Research over the last decade has demonstrated that the regulated packaging of DNA into chromatin is fundamental to keeping genes in an active/open or a more condensed/inactive conformation. Nucleosomes, the basic repeating unit of chromatin, contain two molecules each of canonical histones, H2A, H2B, H3, and H4. These are organized as an H3–H4 tetramer associated with two H2A–H2B dimers. The NH2 termini of histones protrude from the nucleosome, and are the target for a wide array of covalent modifications including acetylation, methylation, and phosphorylation. These modifications are applied and removed in a highly specific manner to generate what has been described as the histone code (Jenuwein and Allis 2001). This code is, in turn, read by chromatin-associated factors. For example, individual acetylated lysine residues are recognized by factors with bromodomains and methylated lysines by chromodomain-containing proteins. Additionally, the action of ATP-dependent chromatin remodeling activities can displace nucleosomes altering the accessibility of DNA within chromatin templates (Flaus and OwenHughes 2001). While most of this work has focused on protein-encoding genes transcribed by RNA polymerase II, more recent studies, including one by Earley et al. (2006) in this issue of Genes & Development, are aimed at elucidating the role that chromatin plays in determining the activity status of the genes that encode ribosomal RNAs (rRNAs). Eukaryotic genomes contain many rRNA gene copies, ranging from hundreds to thousands in some plants, organized in tandem arrays. rRNA genes are transcribed by RNA polymerase I (Pol I) into a precursor RNA (prerRNA) that encodes the three largest RNA components of ribosomes. Pre-rRNA coding sequences are separated by intergenic spacers (IGS) that can range in size from 3 kb in yeast to 30 kb in mammals. Pre-rRNA synthesis is regulated by elements including promoters, transcriptional enhancers, and terminators that are located within the IGS (Grummt 1999). Transcription of rRNA gene arrays results in formation of a nucleolus; consequently, they are termed nucleolar organizer regions (NORs). Importantly, not all NORs are transcriptionally active. Species with multiple NORs can vary the active proportion. Pre-rRNA is matured into 18S, 5.8S, and 28S rRNA by a precisely ordered series of events that includes both cleavages and targeted base modifications. These are required to ensure correct folding of rRNAs for ribosome assembly and function. These multiple steps in ribosome biogenesis require a bewildering array of proteins and small nucleolar RNAs that converge on transcriptionally active NORs, forming such a high concentration of ribonucleoprotein complexes that nucleoli are the most prominent feature of the eukaryotic nucleus. The electron micrographs of Miller and Beatty (1969) demonstrated that the coding regions of active repeats are fully loaded with Pol I. rRNA gene transcription accounts for ∼50% of nascent RNA synthesis in a cell. This high density of transcription and the recent demonstration that it is tightly coupled to pre-rRNA processing (Granneman and Baserga 2004) argues that rRNA gene chromatin needs to be especially accessible. As cells approach metaphase, Pol I transcription is actively shut down and the nucleolus disappears. It is at this point that the specialized nature of active rRNA gene chromatin is most dramatically revealed by the appearance of NORs as secondary constrictions on metaphase chromosomes (McClintock 1934).