RNA silencing is a complex and highly conserved regulatory mechanism that is now known to be involved in such diverse processes as development, pathogen control, genome maintenance and response to environmental changes. Since its recent discovery, RNA silencing has become a fast moving key area of research in plant and animal molecular biology. Research in this field has greatly profited from recent developments in novel sequencing technologies that allow massive parallel sequencing of small RNA (sRNA) molecules, the key players of all RNA silencing phenomena. As researchers are beginning to decipher the complexity of RNA silencing, novel methodologies have to be developed to make sense of the large amounts of data that are currently being generated. In this review we present an overview of RNA silencing pathways in plants and the current challenges in analysing sRNA data, with a special focus on computational approaches.