A recent article by Song in the Journal of Infection systematically analyzed the global spatiotemporal distribution and transmission routes of H6 subtype avian influenza viruses (AIVs), revealing their widespread circulation among wild birds and potential for cross-species infection in mammals. The H5N1 subtype of AIV is circulating globally in wild birds and poultry, with demonstrated transmission to multiple mammalian species and established spread in dairy cattle, elevating public health concerns. Beyond such highly pathogenic AIVs (HPAIVs), several low pathogenic subtypes (LPAIVs), including H9N2, H10N8, H10N3 and H3N8, have also caused human infections. Insufficient surveillance and resources dedicated to LPAIVs compared to HPAIVs increase the risk that a future “Disease X” could emerge from an LPAIV. Globally distributed in wild birds, H6Ny subtype AIVs have limited direct impact on avian health but act as significant genetic donors in natural reservoirs, facilitating reassortment and expanding AIV diversity. Notably, H6Ny viruses can cross species barriers to infect mammals, including humans, as confirmed by a human H6N1 case in Taiwan in 2013 and a human-origin H6N6 strain from Vietnam documented in 2023. Thus, the widespread circulation and reassortment of H6Ny viruses are likely to generate mammalian-adapted strains; the central question is not if, but when and under what conditions this will occur.