The intranasal administration of siRNA has opened new vistas in drug delivery and respiratory therapy. In this strategy, synthetic siRNA with or without chemical modifications can be applied intranasally. Various delivery vehicles have been tested and optimized. With a few exceptions, all promote significant uptake of siRNA into the lung tissue and offer protection against respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza virus (PIV), and influenza virus. No major adverse immune reaction has been encountered. Nasally applied siRNA remains within the lung and does not have systemic access, as judged by its absence in other major organs such as the lung, liver, heart, and kidney. We provide techniques for using the nose as a specific route for siRNA delivery into the lung of laboratory animals, which has enormous potential for clinical applications.