The repair of DNA double-strand breaks (DSBs) is a complex, tightly regulated process. Small noncoding RNAs, such as miRNAs and siRNAs, play many diverse regulatory roles, but their functions in DSB repair have remained largely unexplored. Qi and colleagues have now examined the repair of Arabidopsis thaliana DSBs and report that small RNAs of ∼21 nucleotides in length, derived from both sense and antisense sequences flanking DSBs, are upregulated following DNA damage. Termed DSB-induced small RNAs (diRNAs), their production depends on the kinase ATR, which promotes DNA repair in response to single-stranded DNA, and RNA polymerase IV, which transcribes siRNAs in plants. RNA-dependent RNA polymerases that produce double-stranded RNA (dsRNA) from single-stranded RNA are also necessary for diRNA production, as are Dicer-like proteins, which cleave dsRNAs into shorter fragments. Argonaute 2 (AGO2), a component of the RNA-induced silencing complex, binds mature diRNAs, and loss of AGO2 significantly reduces diRNA levels and impedes DSB repair. However, diRNA expression does not affect RNA-directed DNA methylation, histone H2AX phosphorylation, or the levels of key DNA repair proteins, so the mechanism for their effects on DNA repair is still unclear. Importantly, diRNAs were also detected in human cells, where DSB repair depends on Dicer and AGO2. This suggests that diRNAs have an evolutionarily conserved role in DNA repair, and the authors propose their function may be to recruit specific repair factors. (Cell 149, 101–112, 2012)