Gene expression influences many cellular activities, such that for many of us who are interested in biology, studying gene regulation has been a siren song. Although the role that proteins play in this process is well understood, it is becoming clear that small RNAs are also important gene regulatory factors. Small RNAs, including microRNAs (miRNAs) and short interfering RNAs (siRNAs), are components of a RNA-based mechanism of gene regulation found in eukaryotes. siRNAs are utilized throughout the Eukaryota to inhibit viruses and transposable elements. They also play a role in chromosome organization and silencing expression of protein-coding genes. The miRNA branch of RNA-based gene regulation is less widespread; miRNAs are found in plants and animals but are apparently absent in fungi.