Germline stem cells (GSCs) in the Drosophila ovary are an excellent model system in which to study the mechanisms that regulate stem cell maintenance and differentiation. Now, on p. 4265, Yang and co-workers report that Argonaute 1 (AGO1), a protein that is involved in small-RNA-mediated gene regulation, controls the fate of DrosophilaGSCs. Piwi, another Argonaute protein, helps to maintain GSCs by silencing bag of marbles (bam), a gene that is required for GSC differentiation, but do other Argonaute proteins play similar roles? The researchers report that the overexpression of Ago1 leads to GSC overproliferation, whereas its loss causes a reduction in GSC numbers. This result, together with an analysis of the fate of germline clones that lack a functional Ago1 gene, suggests that an AGO1-dependent miRNA pathway probably plays an instructive role in repressing GSC differentiation. Finally,the researchers show that some GSCs partly differentiate in Ago1 bamdouble mutants, which suggests that AGO1 (unlike Piwi) might regulate GSC fate in a bam-independent manner.