Since its emergence in East Asia, H5N1 HPAI has attracted considerable public and media attention because the viruses involved have been shown to be capable of producing fatal disease in humans, which gives rise to the fear that the virus might acquire the capacity for sustained human-to-human transmission and thus cause a global influenza pandemic. Driven by this fear of a possible human pandemic, responses to HPAI outbreaks have generally been top-down, heavy handed interventions which involved the culling of millions of birds at great expense. However, despite determined eradication efforts, outbreaks continue on a regular cycle and in some areas the disease appears to have become endemic. It is also evident that applied control measures have unintended behavioural consequences that undermine their effectiveness because they have negative economic impacts, particularly with respect to the livelihoods of smallholder poultry keepers and other actors engaged in poultry value chains. This paper presents the results of an interdisciplinary HPAI research project carried out in the greater Mekong sub-region (GMS).