In most eukaryotes, histone and DNA modifications are responsible for the silencing of genes integrated in heterochromatic sequences, as well as the silencing of pericentromeric repeats and transposable elements themselves. But the mechanisms that guide these modifications to heterochromatin during the cell cycle have been elusive. RNA interference takes advantage of heterochromatic transcription to process small RNAs and recruit enzymes required for both histone and DNA modifications, and is one such mechanism that has been identified. The processes are best understood in fission yeast and plants, but recent work in mammalian cells, especially in the germline, suggests these mechanisms may be highly conserved.