The study of Schistosoma species has undergone a dramatic change in recent years mainly due to transcriptome, proteome, and genome analyses. In order to better understand the biology of the parasite and to develop new and more efficient/specific drugs, scientists have now the task to translate genetic information into functional data. The present paper aims to review the use of RNA interference (RNAi), a versatile technique used in gene silencing, for the dissection of the cellular/molecular biology of Schistosoma spp. In addition, we will review information on the recent development of a new generation of RNA-based drugs. Examples of specific experimental approaches will be presented and discussed, such as identification of gene function, development of therapies by targeting eggs, miracidia (as a strategy for environmental use), sporocysts (for infestation control in the intermediate host), and schistosomula/adult worms (as a treatment strategy). Furthermore, some of the main advantages, drawbacks, and future directions of these new applications and techniques will also be discussed.