RNA interference is a biological process for gene silencing that can be harnessed for the development of new drugs. However, a major obstacle to the use of small interfering RNAs (siRNAs) as therapeutics is their delivery across the plasma membrane of cells in vivo. A range of solutions for this challenge have been described, including cationic lipids, high-pressure injection, viral vectors, and chemical modifications of the siRNAs. This chapter describes cationic lipid delivery of siRNAs to adult mice.