RNA interference (RNAi) is a unique gene regulation mechanism in eukaryotic organisms. It is typically mediated by short interfering RNAs (siRNAs), microRNAs (miRNAs), and recently discovered PIWI-interacting RNAs (piRNAs). In plants, RNAi is also called post-transcriptional gene silencing (PTGS), in which diverse small RNAs are utilized to defend against viral or bacterial infection, and to modulate endogenous gene expression and chromatin structure. Many PTGS-related genes have been identified by genetic screens in plants, including suppressor of gene silencing 2 (SGS2, also called RDR6), SGS3, hua enhancer 1 (HEN1), dicer-like 4 (DCL4), and argonaute 1 (AGO1). For most of these proteins, their potential functions have been uncovered through sequence similarity searches and protein domain examinations. For instance, SGS2 encodes a RNA-dependent RNA polymerase (RdRp); HEN1 is a RNA methyltransferase with a double-stranded RNA-binding motif; DCL4 is a Dicer for producing siRNAs; and AGO1 is a RNA slicer with PIWI and PAZ domains. Their retrieved homologs in other organisms including mammals, Drosophila and the nematode Caenorhabditis elegans have also been shown to be crucial in RNAi pathways, indicating an evolutionary conservation for RNAi mechanisms. However, one exception is the SGS3 protein, whose specific function remains unclear so far.