Influenza A is a highly contagious respiratory virus in constant evolution and represents a threat to both veterinary and human public health. IA viruses (IAVs) originate in avian reservoirs but may adapt to humans, either directly or through the spillover to another mammalian species, to the point of becoming pandemic. IAVs must successfully be able to (i) transmit from animal to human, (ii) interact with host cells, and (iii) transmit from human to human. The mechanisms by which viruses evolve, cause zoonotic infections, and adapt to a new host species are indeed complex and appear to be a heterogeneous collection of viral evolutionary events rather than a single phenomenon. Progress has been made in identifying some of the genetic markers mainly associated with virulence and transmission; this achievement has improved our knowledge of how to manage a pandemic event and of how to identify IAVs with pandemic potential. Early evidence of emerging viruses and surveillance of animal IAVs is made possible only by strengthening the collaboration between the public and veterinary health sectors.