The development of effective therapies for lethal diseases is highly desired. RNA interference (RNAi) is a post-transcriptional gene silencing mechanism preserved during evolution. Intriguing aspect of the RNAi is its attractive potential therapeutic value, because of their ability to target any disease for which the genetic basis is known. As the use of RNAi for gene manipulation-tool has been extensively studied, RNAi technology has not only become a powerful tool for functional molecular biology, but also represents a promising novel therapeutic option for treating deseases. In this review, we will describe these studies that demonstrate the feasibility of using RNAi and discuss potential strategies for improving gene silencing. We will also discuss the recent consideration and challenges of using RNAi based technologies.