Small regulatory RNAs are integral players in eukaryotic gene regulation, and are involved in numerous developmental and pathological pathways. Although the field has been making remarkable progresses in recent years, it still has a number of seminal questions. We need to understand how cell signaling pathways are connected to small RNA pathways, how small RNAs are regulated and function during cell fate transition, how small RNAs interact with subcellular compartments, if and how they are transported between cells, and how small RNAs participate in immune response. We also need to gain a systemic view of small RNAs and their targets in the context of gene network, and to understand their involvements in human diseases, not just cancer but also other genetic and metabolic disorders. This conference brings together scientists studying diverse animal and plant model organisms, which will offer an opportunity to understand the mechanism and function of small RNAs in an evolutionary and physiological context. The symposium will also bridge the gaps between fundamental knowledge, clinical needs and technical development by addressing issues such as small RNA involvement in diseases, in vivo delivery of RNA and technical challenges in RNA detection at single-molecule and single-cell levels. Compared with other conferences on RNA, this conference is unique in that it focuses on small regulatory RNAs, yet it is highly diverse in research approaches and biological systems. It will serve as a central forum for the small RNA community.