The anti-RNA virus activity of polyoxometalates (POM) is reviewed, with a special emphasis on the anti-respiratory virus activities. There are many causative agents of acute viral respiratory infections; and it is rather difficult to identify the relevant agent in a given case by rapid clinical means. During acute progress of infection before the definitive diagnosis is obtained physicians need to prescribe certain broad spectrum anti-viral drugs. A titanium containing polyoxotungstate, PM-523 exhibited potent anti-influenza virus (FluV) A and anti-respiratory syncytial virus (RSV) activities in vitro. Therapeutic effect of FluV A infected mice with aerosol inhalation of PM-523 was proven. A vanadium substituted polyoxotungstate, PM-1001 has antiviral activity against FluV A, RSV, parainfluenza virus (PfluV) type 2, Dengue fiver virus, HIV-1 and SARS coronavirus in vitro. Thus, POMs have been proven to be broad spectrum and non-toxic anti-RNA virus agents in both in vitro and in vivo experiments and are promising candidates for first-line therapeutics in acute respiratory diseases.