The multiple viral infections outbreaks in the last decade has posed a pandemic risk. These infectious disease lead to significant morbidity responsible for intensive care unit hospitalization in about 10% cases and high mortality. Several efforts are currently made to find a treatment for managing these viral infection. Interestingly, many anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on respiratory viral infection during in vitrostudies , animal models as well as few cases series. In most respiratory viral infection patients a pro-inflammatory status with high levels of interleukin (IL)-1B, IL-1 receptor (R)A and tumor necrosis factor (TNF)-α has been demonstrated. Additionally, high levels of IL-6 and TNF-α have been observed in patients requiring intensive-care-unit hospitalization. There has been abundant efforts in the development of new drugs to fight these infections. The increasing knowledge about the pathophysiology of viral infection is leading to consider some anti-rheumatic drugs as potential treatment options. Agents, such as hydroxychloroquine and chloroquine might have a direct anti-viral effect. A wide range of anti-rheumatic drugs has shown anti-viral activity, but they are not yet approved these indications. In the present talk, I will discuss known anti-viral properties of immunosuppressants and their potential role in the treatment of respiratory viral infection.