The phenomenon of RNA interference or RNAi was discovered in the 1990’s as a means to epigenetically silence genes in a highly specific manner. It turns out that the key effectors of RNAi are siRNAs. Today, siRNAs are routinely used in the biomedical field to trigger RNAi and study gene function. siRNAs have a size of about 22 nucleotides, and they are produced from double-stranded RNA precursor molecules of varying length and origin. Precursor RNAs are processed by members of the RNase III family of Dicer or Dicer-like (DCL) enzymes. Resulting siRNAs are duplex in structure. They are then incorporated into a RNA-induced silencing complex (RISC) composed of numerous cellular proteins. Incorporation is coupled with duplex unwinding to generate single-stranded siRNAs, of which only one strand of the pair remains associated with RISC. The retained RNA strand acts as a guide for RISC to find mRNA transcripts with complementary sequence. If such mRNA molecules are found, the base pairing interactions between siRNA and mRNA lead to transcript cleavage and degradation. siRNAs can also guide factors that methylate histones and DNA, resulting in transcriptional silencing.