Three worldwide influenza pandemics were reported in the 20th century: in 1918, 1957 and 1968. All three pandemics were caused by different sub-types of Influenza A viruses: H1N1, H2N2 and H3N2 respectively. In early March 2009, the first cases of influenza -like illness (ILI) were reported from Mexico. This strain was identified as influenza A/ H1N1 strain. Pandemic (H1N1) 2009 influenza most commonly causes a self-limited illness, however, significant morbidity and mortality were reported in the young, the obese and in pregnant women. The drugs of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitors, Oseltamivir and Zanamivir. While a few cases of Oseltamivir-resistance are reported, these isolates still retained their susceptibility to the inhaled Neuraminidase inhibitor, Zanamivir. Pandemic (H1N1) 2009 influenza virus is routinely resistant to the adamantanes: Amantadine and Rimantadine. These agents should not be used for the treatment or prophylaxis of pandemic (H1N1) 2009 influenza. The FDA recently approved the emergency use of Peramivir, an intravenous neuraminidase inhibitor, for the treatment of patients with severe influenza. We discuss the use of available antivirals, as well as the effectiveness of adjunctive therapies with immunomodulatory and anti-inflammatory agents, such as immunoglobulins and statins, for the treatment and management of patients with severe H1N1 influenza. This review summarizes the recent patents for the use of antivirals in treatment of severe influenza.