Since its emergence in China in 1996, highly pathogenic avian influenza virus subtype H5N1 has spread across Asia, Africa, and Europe. Countries had to promptly implement control and prevention measures. Numerous research and capacity building initiatives were conducted in the affected regions to improve the capacity of national animal health services to support the development of risk-based mitigation strategies. This paper reviews and discusses risk assessments initiated in several South-East Asian and African countries under one of these projects. Despite important data gaps, the risk assessment results improved the ability of policy makers to design appropriate risk management policies. Disease risk was strongly influenced by various human behavioral factors. The ongoing circulation of HPAIV H5N1 in several Asian countries and in Egypt, despite major disease control efforts, supports the need for an interdisciplinary approach to development of tailored risk management policies, in accordance with the EcoHealth paradigm and the broad concept of risk governance. In particular, active stakeholders engagement and integration of economic and social studies into the policy making process are needed to optimize compliance and sustainable behavioral changes, thereby increasing the effectiveness of mitigation strategies.