Epigenetic regulation of gene expression has become relevant to nearly all areas of biomedical research. The emergence of technologies that allow for examination of the epigenome combined with identification of key protein complexes that mediate the myriad chromatin modifications that occur have greatly enhanced the versatility and efficacy of tools with which to study normal development and disease states. The evolutionarily conserved polycomb group genes (PcG) have been identified as a predominant mechanism by which gene silencing occurs during development, differentiation, and disease. While molecular events that target PcG complexes have been well defined in some non-vertebrate models, the details of locus specificity and functional diversity of mammalian PcG proteins have not yet unresolved. Here we discuss recent findings that offer novel mechanistic events and add complexity to our understanding of PcG function in vertebrates. J. Cell. Physiol. 226: 1719–1721, 2011. © 2010 Wiley-Liss, Inc.