The Greater Mekong Sub-region (the geo-political region comprising Cambodia, Laos, Myanmar, Viet Nam, Thailand, and Southern China) is undoubtedly undergoing a dramatic shift in virtually any of its aspects, ranging from orthodox economic development, through resources management, to institutional capacity building and regionalisation. Among the myriad of issues rising from such new and/or exacerbating tensions, cross-border environmental governance is too often marginalised in the integration discourse, and with a still insufficient awareness among the local population, the risk of politicisation and exploitation is high. Given the average level of institutional development at both local and national level, accountability and impunity concerns become paramount. This research project examines the nexus between the regionalisation process and the management of natural resources in the sub-region. The perspective used is twofold: the regional response to the challenge embodied by the Mekong River Commission (MRC) and partners, and the local reaction on the ground. Such approach provides insights on the interdependency of, respectively, governance experimentation and change adaptation, with the ultimate goal of considering the possibility to establish a sustainable development framework modelled on the GMS experience.