The last 110 years have seen four influenza A pandemics, where viruses have emerged from mammals or birds with the ability to transmit and cause disease in human populations. Since 2021, a high-pathogenicity strain of avian influenza, H5N1, has caused a panzootic (pandemic of animals), with global spread in wild birds, resulting in frequent spillovers into farmed poultry and into mammals, including mammal species not previously known to be affected by influenza A. This has created increased opportunity for reassortment, mutation, human infection, and potential adaptation to transmit. The risk to humans and the impact are difficult to quantify but of mounting concern to public health bodies. Here, we examine the risk of an H5N1 pandemic emerging and spreading in humans and the potential impact of an H5N1 pandemic.