Sponsored by Novartis Institutes for BioMedical Research. MicroRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) act as guide RNAs to direct gene-silencing pathways in eukaryotes. These silencing pathways require related core components to process and utilize the guide RNAs. Nonetheless, they have evolved to perform different biochemical functions, mediating either transcriptional or posttranscriptional silencing important for numerous endogenous gene-regulatory programs as well as viral resistance, transposon suppression, centromere function, and programmed genome rearrangement. The aim of this meeting is to report on recent advances in understanding both the molecular mechanisms of siRNA- and miRNA-directed silencing and the biological functions of these mechanisms.