Influenza viruses of animals can cross species and infect humans. In this issue of Cell Host & Microbe, Zhang et al. (2015) and Tzarum et al. (2015) describe crystal structures and receptor-binding properties of hemagglutinins of avian-origin H10N8 and H6N1 influenza viruses. Human infections with these viruses are not associated with a switch favoring human receptor binding.