Influenza viruses are etiological agents of deadly flu that continue to pose global health threats, and have caused global pandemics that killed millions of people worldwide. The global crisis involving the avian H5N1 and more recently porcine H1N1 influenza both provide compelling reasons for accelerate fast track development of novel antiviral drugs against the potential pandemic virus. The availability of neuraminidase inhibitors such as oseltamivir (tamiflu) improves our ability to defend against influenza viruses, but the incidences of tamiflu-resistance are on the rapid rise. Nucleic acid-based antiviral drugs are promising classes of experimental antiviral drugs that have been shown in preclinical studies to be effective against seasonal and avian influenza viruses. The potency and versatility of these drugs make them potential candidates to be used in seasonal and pandemic influenza scenarios. Here we review recent patent activity in the development of nucleic acid based drugs directed at influenza. The review will assess the recent patents, research and development of antisense oligonucleotides, immunomodulating RNA and the most rapidly developing area, the exploitation of small interfering RNA for the prevention and treatment of influenza infection.