The finding that sequence-specific gene silencing occurs in response to the presence of double-stranded RNAs has had an enormous impact on biology, uncovering an unsuspected level of regulation of gene expression. This process, known as RNA interference (RNAi) or RNA silencing, involves small non-coding RNAs, which associate with nuclease-containing regulatory complexes and then pair with complementary messenger RNA targets, thereby preventing the expression of these mRNAs. Remarkable progress has been made towards understanding the underlying mechanisms of RNAi, raising the prospect of deciphering the 'RNAi code' that, like transcription factors, allows the fine-tuning and networking of complex suites of gene activity, thereby specifying cellular physiology and development.