Cell fate decisions can be maintained during long periods of developmental time by stable states of gene expression. The Polycomb group and trithorax group proteins of Drosophila are key transcriptional regulators that maintain stable expression states during development. Recent advances in knowledge about individual Polycomb group and trithorax group proteins, their mechanisms of action, and potential homologs in mice and humans are contributing to a greater understanding of their roles in gene expression and development.