Abstract: RNA interference (RNAi), which has become the first method of choice to suppress gene expression in vitro, is a conserved biologic response to double-stranded RNA that resulted in the sequence-specific silencing of target gene expression. Recently, more than 100 studies using synthetic small interfering RNAs in mammals have been published. These reports demonstrate that RNAi is also a powerful tool for in vivo research and may become an effective therapeutic tool. This review will focus on the influential factors and experimental design in the in vivo use of RNAi.