RNA interference (RNAi) has become a powerful tool for the knockdown of target gene expression and subsequent phenotypic analysis of gene function in mammalian cells in culture. Critical to the success of any small inhibitory RNA (siRNA)-mediated RNAi knockdown in mammalian cells is the efficient delivery of the siRNA to those cells. This chapter describes the use of popular cationic lipid?polymer-based transfection reagents for in vitro siRNA delivery and includes a general protocol with special emphasis on key transfection parameters important to the success of siRNA delivery.