The generation of pandemic influenza A viruses of the previous century as well as that of the current influenza A/H1N1/2009 pandemic appear to be governed and preceded by reassortment events in other mammalian species. So far, it could not be shown that transmission of avian influenza viruses to humans will directly cause a pandemic. Zoonotic transmissions of avian and also of porcine influenza viruses of diverse subtypes have been repeatedly described. However, these events did not lead to further spread and establishment of these viruses. This is in contrast to the current A/H1N1/2009 viruses which already have started to outcompete seasonal human influenza viruses. The actual molecular key factors required for a successful exchange of genome segments between different influenza virus strains and which factors foster the consecutive spread of certain reassortant viruses in the human population remain to be pinpointed. It has been elucidated so far that newly introduced genome segments need to be compatible with both the remaining original segments and the human hosts.