The rapid evolution and spread of the highly pathogenic avian influenza HPAI A (H5N1) viruses is a global threat not only to poultry farming and wildlife conservation but also to the public health communities as a result of the animalhuman (zoonosis) cases of its genetic reassortant (H5N8) recently detected in seven poultry workers in Russia. However, considering the increased fatalities in poultry and wild birds, and the potential of zoonosis in escalating to a deadly pandemic, there is a need for concerted efforts between human and animal health institutions such as World Health Organization and World Organization for Animal Health, and wildlife conservation communities for birds. This is to mitigate the threat occurring at the humanenvironment-animal interface. In this commentary, we explicate the evolution and spread of HPAI A (H5N1) viruses and recommend some measures that could be taken to mitigate this threat, particularly on its pandemic potential.