RNA interference (RNAi) is a powerful, quick, and easy technique to reduce the expression of a particular gene. However, investigators need to consider several steps for the experiments, including the design of the siRNA, an efficient delivery method, and a means for monitoring the biological effects of the siRNA introduced. Adipocytes have long been recognized as one of the most difficult cell types in which to perform gene delivery. In this chapter, three distinct transfec-tion methods to obtain high efficiency of gene delivery and gene knockdown are described. The transfection efficiency of siRNA and shRNA is also compared.