Future food security poses many challenges and with increasing prosperity and demand for meat, the emerging but largely unregulated trade in livestock and their products from developing countries in South-East Asia and particularly the Mekong region, pose enormous risks of transboundary disease epidemics. However this is a challenge that should be met as substantial improvements in large ruminant production through appropriate knowledge-based interventions can potentially move the largely rural smallholder populations of Lao PDR and Cambodia from subsistence to a productivity focus, offering a new pathway for poverty alleviation. Large development projects have been implemented in the Mekong region to facilitate this process and research is needed to define problems, identify and test solutions, and then suggest the most appropriate delivery mechanisms for promulgating the interventions that are most sustainable. Animal health aid projects are needed to improve livestock productivity, minimize risk to trade and human health and enhance the capacities of countries where there are significant gaps in the provision of veterinary services. Improving large ruminant production, particularly through forages technology and infectious disease risk management including village-level biosecurity, provides a potential driver of foot and mouth disease (FMD) control and eventual eradication in the region. A perspective on issues involved in Australian aid projects addressing regional animal health research and development and a checklist of strategies to consider when designing and managing such projects is provided.