The past 25 years have seen a noncoding RNA revolution that was initiated by the discovery of the lin-4 microRNA (miRNA) in the nematode Caenorhabditis elegans. Here, I will report how we have used C. elegans to dissect rules of miRNA target engagement, regulation, and physiological function in vivo through genetic, biochemical and genomics approaches. I will focus on our recent identification and ongoing characterization of a novel physical interaction partner of Argonaute, the miRNA-binding protein that is at the core of the miRNA-induced Silencing Complex (miRISC). The new factor, important for animal fertility, binds Argonaute loaded with miRNAs but devoid of the GW182 miRISC effector protein. Hence, we propose, and test in ongoing experiments, that it plays a role in Argonaute target binding, recycling, or quality control.