RNA interference is a highly conserved pathway mediating sequence-specific RNA degradation. In plants, the short RNA intermediates of this pathway can also drive transcriptional silencing of target genes by DNA methylation. Until recently, there was no evidence that a similar pathway operated in mammals; two new studies suggest that small RNAs can direct DNA methylation and chromatin modification in human cells. Although further investigation is required to determine how widespread RNA-directed DNA methylation is in mammals, the findings raise the possibility that this pathway, far from being merely a curiosity of plant systems, is a conserved mechanism for control of gene expression.