Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs, various types of siRNAs and piRNAs. These classes differ in their biogenesis, modes of target regulation and in the biological pathways they regulate. However, there is also a growing realization that these distinct small RNA pathways are interconnected. These pathways functions in RNA-based immunity, developmental gene regulation, transcriptional silencing, and genomic stability. The aim of this meeting is to explore the similarities and differences between RNA silencing pathways, to probe their underlying molecular mechanisms, to learn—by illustrative examples—the logic behind RNA-guided regulation of gene expression, and to explore new methods for harnessing these mechanisms for gene discovery and therapeutics applications.