Small double stranded RNA molecules known as small interfering RNA (siRNA), initially identified for their role in the guide sequence in the effector complex of the RNA interference pathway, now represent a promising new class of therapeutic agent with potentially important clinical applications for the prevention and treatment of viral disease. siRNA with its ability to harness the cells own gene-silencing apparatus in a highly adaptable and sequence specific manner has demonstrated unprecedented anti-gene activity. This review highlights the key chemical and biological parameters of this technology and its application in viral suppression, particularly in the respiratory tract. This treatment site represents both an important opportunity to establish clinical exposure for the technology, and an important challenge to provide an additional layer of protection against highly threatening influenza epidemics and potential pandemics.