The amount of knowledge about new classes of small RNA molecules has expanded at a breathtaking pace in the last few years. This expansion is mainly due to the advent of new, advanced, technologies to profile RNAs, such as massively parallel signature sequencing (MPSS) and 454 pyrosequencing. Until recently, rare RNA species had only a small chance of being discovered because of the small-scale sequencing approaches used. The vast amounts of data presently generated and coupled with computational analysis allow a yet unprecedented exploration of the heterogeneity of 20- to 30-nt-long small RNAs and their role in post-transcriptional gene regulation. The continual discovery of new small RNA species suggests that we are only just beginning to appreciate the complexity of small RNAs and their functions. Extended studies on these new exciting classes of small RNAs, which were previously thought to be mere degradation products, will undoubtedly uncover novel roles for these tiny molecules in health and disease.