For the first time in human history virologists have the knowledge about the avian origin of pandemic influenza A viruses. Furthermore, in the last two decades a new class of anti influenza drugs, the neuraminidase inhibitors (NIs), has been developed from an academic discovery to a series of antiviral drugs to be used in the clinic. At present vaccinologists are producing influenza A (H5N1) vaccines to be stockpiled alongside the NIs to combat the first wave of an anticipated influenza pandemic. Studies from the 1918 infection calamity, the Spanish influenza, and the succeeding pandemics of 1957 and 1968, all caused by avian influenza A viruses, have shown how quickly such a virus can mutate to become less virulent (starting with 50% case fatality) and more infectious. Such a mutation cluster could lead to a rapid increase in world deaths, currently 170, to many millions. However there are optimistic analyses: judicious and swift application of NIs, vaccine and hygiene to an outbreak epicentre, most likely in South-East Asia, could break the chain of transmission.