During oogenesis, female animals load their eggs with messenger RNAs (mRNAs) that will be translated to produce new proteins in the developing embryo. Some of these maternally provided mRNAs are stable and continue to contribute to development long after the onset of transcription of the embryonic (zygotic) genome. However, a subset of maternal mRNAs are degraded during the transition from purely maternal to mixed maternal-zygotic gene expression. In Drosophila, two independent RNA degradation pathways are used to promote turnover of maternal transcripts during the maternal-to-zygotic transition . The first is driven by maternally encoded factors, including SMAUG , whereas the second is activated about 2 hr after fertilization, coinciding with the onset of zygotic transcription. Here, we report that a cluster of zygotically expressed microRNAs (miRNAs) targets maternal mRNAs for turnover, as part of the zygotic degradation pathway. miRNAs are small noncoding RNAs that silence gene expression by repressing translation of their target mRNAs and by promoting mRNA turnover. Intriguingly, use of miRNAs to promote mRNA turnover during the maternal-to-zygotic transition appears to be a conserved phenomenon because a comparable role was reported for miR-430 in zebrafish . The finding that unrelated miRNAs regulate the maternal to zygotic transition in different animals suggests convergent evolution.