DNA methylation, histone deacetylation, and methylation of histone H3 at lysine 9 are the three best-characterized covalent modifications associated with a repressed chromatin state. Recent advances highlight an essential, intricate web of interactions among these processes, generating a self-reinforcing, self-perpetuating cycle of epigenetic events that lead to long-term transcriptional repression. Histone deacetylation and methylation at lysine 9 of H3 might also contribute to the establishment of DNA methylation patterns, a long-standing mystery in epigenetics. What's more, recent clues suggest a potential link between CpG methylation and other histone modifications. A complex picture is emerging in which DNA methylation and histone modifications work hand-in-hand as parts of an epigenetic program that integrates gene-silencing networks within the cell.