The Department for Environment, Food and Rural Affairs (Defra) has monitored epidemiologic developments following outbreaks of H5N1 in Asia since the beginning of 2004 and publishes risk assessments as the situation evolves. The U.K. applies safeguard measures that reflect EU rules to enable imports to continue when they present negligible risk. Defra risk assessments (RA) identify possible pathways by which the H5N1 virus may be introduced to the U.K. These assessments provide a basis for identifying appropriate surveillance activities to ensure early detection, should the virus be introduced, and disease control measures to be taken, should the virus be detected in the U.K. Nevertheless, these assessments have highlighted that many fundamental uncertainties still remain. These uncertainties center on the geographic and species distribution of infection outside Asia and the means of dissemination of the virus. However, the evolving developments demonstrated that regulatory decisions had to be made despite these uncertainties. Improvements in our current RA abilities would greatly benefit from systematic studies to provide more information on the species susceptibility, dynamics of infection, pathogenesis, and ecology of the virus along with possible pathways by which the H5N1 virus may be disseminated. Such an approach would assist in reducing uncertainties and ensuring that regulatory risk management measures are regularly reviewed by taking into account the most recent scientific evidence. The likelihood of the persistence of H5N1 outside Asia in the coming years and the effects of control programs in Asia and other affected regions to reduce the prevalence of infection are also important factors.