Small-RNA-guided gene regulation has emerged as one of the fundamental principles in cell function, and the major protein players in this process are members of the Argonaute protein family. Argonaute proteins are highly specialized binding modules that accommodate the small RNA component - such as microRNAs (miRNAs), short interfering RNAs (siRNAs) or PIWI-associated RNAs (piRNAs) - and coordinate downstream gene-silencing events by interacting with other protein factors. Recent work has made progress in our understanding of classical Argonaute-mediated gene-silencing principles, such as the effects on mRNA translation and decay, but has also implicated Argonaute proteins in several other cellular processes, such as transcriptional regulation and splicing.