RNA interference (RNAi) is a process through which double-stranded RNA induces the activation of endogenous cellular pathways of RNA degradation, resulting in selective and potent silencing of genes that have homology to the double strand. Much of the excitement surrounding small interfering RNA (siRNA)-mediated therapeutics arises from the fact that this approach overcomes many of the shortcomings previously experienced with alternative approaches to selective blocking that use antibodies, antisense oligonucleotides or pharmacological inhibitors. Induction of RNAi through administration of siRNA has been successfully applied to the treatment of hepatitis, viral infections, and cancer. Increased success in addressing issues of siRNA delivery and efficiency will permit this approach to evolve as a new paradigm in clinical therapeutics. In this chapter, we present applications of RNAi in tissue injury, and the possibilities of using this highly promising approach in the context of transplantation.