In 2009, we have been experiencing a new pandemic of novel influenza virus type A (H1N1) infection. The human beings still face the threat of highly pathogenic avian influenza A (H5N1) virus. Many patients with influenza virus infection have died due to severe complications even though receiving intensive care. This suggests the need for new treatment strategies of severe influenza-associated complications. In cases of severe influenza-associated complications, pathological manifestations are as a result of complex biological consequences, such as apoptosis induction, macrophage activation, oxidative damage and increased production of pro-inflammatory cytokines. Recent studies have revealed that the pathogenesis of severe influenza-associated complications involves not only the virus replication-mediated apoptotic cell death in the infected cells but also non-infected cell injury by toxicity of reactive oxygen species derived from macrophages phagocytosing apoptotic cells, and that pro-inflammatory cytokines produced by the virus-infected host cells play a critical role in the activation of macrophages. These findings provide a possibility that an agent with antiviral and antioxidant activities can be a drug of choice for the treatment of patients with severe influenza-associated complications. Selected antioxidants, such as pyrrolidine dithiocarbamate, N-acetyl-L-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin and certain types of flavonoids, possess both activities. The combination of antioxidants, such as superoxide dismutase and N-acetyl-L-cysteine, with antiviral drug ribavirin synergistically reduced the lethal effect of influenza virus infection. Accumulating a number of evidence highlights a potential of selected antioxidants for treatment of severe influenza-associated complications and a possibility that combination of antioxidants with current anti-influenza drugs can improve conventional influenza chemotherapy.