Since Dr. Sidney Brenner first used it as an animal model system, the round worm Caenorhabditis elegans has significantly contributed to our understanding of important biological processes. Among them, the discovery in the 1990s of new gene silencing pathways orchestrated by tiny non-coding RNAs created a new field of research in biology. In this review, we will discuss the key players of the RNAi pathways in C. elegans and particularly the Argonaute genes, an impressive gene family of 27 members important in many aspects of these pathways.