Reducing vulnerability to environmental change must be a key component of any strategy for sustainable development. We consider the situation of the nations of the Lower Mekong, namely Cambodia, Lao PDR, and Vietnam, focusing on the threat of climate change. We distinguish between physical vulnerability, characterized in terms of spatial exposure to hazardous events, and social vulnerability, which is a function of the social conditions and historical circumstances that put people at risk. As vulnerability is a dynamic condition, we frame the assessment in terms of the processes and trends that are shaping current patterns of vulnerability and resilience. The nations of the Lower Mekong face a range of potential trends in climate, with changes in the incidence of flooding, variability in water availability, the occurrence of drought and heat stress, the frequency and/or intensity of tropical cyclones, and, in coastal areas, sea-level rise posing the major risks. A baseline assessment of the social, economic, and political trends that are influencing present-day levels of social vulnerability highlights the fact that poverty is the largest barrier to developing the capacity to cope and adapt effectively with change. The situation of the poorest members of society is being adversely affected by trends in inequality, disparities in property rights, dismantling of agricultural cooperatives, unions, and various forms of financial support and changes in social structure and institutions. We identify an important tension that can exist between efforts aimed at improving the general economic situation and what is needed to improve resilience to climate stress, particularly among the rural poor. As far as adaptation is concerned, there are lessons for other regions in the traditional approaches developed within the Lower Mekong, as these nations have a rich history of managing their dynamic natural environment.