Developmentally regulated genome rearrangements (DRGR)—processes that alter genomes either in specific cells or during specific life cycle stages—are widespread throughout eukaryotes. This contrasts with the view that genome structure and content remain essentially constant throughout an organism's life cycle. Here we review three categories of developmentally regulated genome processing in eukaryotes: genome-wide rearrangements, targeted rearrangements, and a special case of amplification of ribosomal DNA genes. Mapping these types of DRGR onto eukaryotic phylogeny indicates that each type of processing is found in multiple independent lineages. We propose that such genome rearrangements were present within the last common ancestor of extant eukaryotes, and that future research will yield evidence of homologous epigenetic mechanisms underlying genome processing among diverse eukaryotes. J. Exp. Zool. (Mol. Dev. Evol.) 304B, 2005. © 2005 Wiley-Liss, Inc.