The roles that RNA molecules play in the regulation of gene expression have only recently begun to come to light. Recent work in this area has uncovered several complex, RNA-mediated networks of gene regulation in eukaryotic systems. One newly discovered mechanism of RNA mediated gene regulation takes place at the level of transcription. In yeast, plant, and mammalian systems, small RNAs targeted to gene promoters can result in a repression of transcription. Small RNA mediated transcriptional silencing has been shown to be operative by changes in chromatin structure at the targeted promoter. Specifically, silencing has been observed to correlate with decreases in certain active-state histone modifications, increases in various certain-state histone methylation marks, and in some instances, DNA methylation at the targeted promoter. These epigenetic remodeling events represent a more stable, heritable form of gene regulation as opposed to the transitory post-transcriptional regulation observed in traditional RNAi mechanisms. Several recent findings have shed light on this newly discovered link between small RNA molecules and epigenetic regulatory machinery, notably in human cells.