In 1918, a strain of influenza A virus caused a human pandemic resulting in the deaths of 50 million people. A century later, with the advent of sequencing technology and corresponding phylogenetic methods, we know much more about the origins, evolution and epidemiology of influenza epidemics. Here we review the history of avian influenza viruses through the lens of their genetic makeup: from their relationship to human pandemic viruses, starting with the 1918 H1N1 strain, through to the highly pathogenic epidemics in birds and zoonoses up to 2018. We describe the genesis of novel influenza A virus strains by reassortment and evolution in wild and domestic bird populations, as well as the role of wild bird migration in their long-range spread. The emergence of highly pathogenic avian influenza viruses, and the zoonotic incursions of avian H5 and H7 viruses into humans over the last couple of decades are also described. The threat of a new avian influenza virus causing a human pandemic is still present today, although control in domestic avian populations can minimize the risk to human health.