Once established, homeotic gene (Hox) expression is maintained in the original pattern by Polycomb-group (PcG) and trithorax-group (trxG) proteins therefore named maintenance proteins (MPs). PcG and trxG proteins maintain silencing and activation of Hox and many other genes, respectively. We provide here a brief overview of genetics and molecular biology of these proteins and of a third class of proteins termed Enhancers of Trithorax and Polycomb (ETP) that are required for both maintenance of silencing and activation of Hox genes. We examine the recruitment of MPs onto maintenance elements (MEs), their role in the regulation of transcription and the epigenetic marks that could provide maintenance. Lastly, we discuss two important roles of PcG proteins in replication of DNA and stem cell renewal and maintenance.