RNA silencing systems are now well established as key components of regulation and control in many eukaryotes including animals and plants. The first flush of discoveries was focused around post-transcriptional regulation. It was anticipated that the small RNA specificity determinants of these silencing systems could be negative switches acting alongside transcription factors control of gene expression during growth, development and responses to external stimuli. More recently the emphasis has shifted. In terms of post-transcriptional regulation, it is now recognized that there are only a few examples in plants and worms in which sRNAs are simple switches. These RNAs are now seen as modulators or fine tuners of post-transcriptional regulation that are often components of negative feedback loops or of control networks in which there are long RNA negative regulators of the sRNAs and secondary sRNAs. The sRNAs can be transported or secreted out of cells and so the RNA mediated control networks may extend beyond one cell. The anticipated potential of sRNA therapeutics has yet to be delivered but they are proving to be a powerful diagnostic tool in cancer and other diseases. A second emerging area is in the link between sRNAs and epigenetic regulation. This link was revealed first from plant work but it is now known in animals in connection with piwi-associated RNAs or piRNAs. These epigenetic sRNAs and piRNAs are certainly important in defense against transposable elements but it is possible that they also influence genetic or epigenetic regulation in other cell types. In this complex array of sRNA functions, growing interest is now devoted also to the crucial role of long noncoding RNAs in processes of gene expression control both at the transcriptional and post-transcriptional levels. The 2013 Keystone Symposia meeting on RNA Silencing will focus on these emerging topics of network control systems and epigenetic regulation by various types of sRNA. The program for this meeting is highly likely to attract a wide variety of investigators, many of whom might not otherwise interact. The focus on RNA silencing in general provides an umbrella under which speakers from different areas of research (e.g., transcriptional regulation, cancer biology, development, epigenetics and virology) are being brought together in an environment that is highly conducive to cross-talk. Emphasis has also be placed on showcasing early stage investigators presenting on the program with a view to promoting the next generation of scientists in the RNA silencing field.