Since the 1990s, energy development has become a major focus of economic cooperation in the Greater Mekong Sub-region (GMS). Based on privatization and deregulation, multinational banks have advocated the establishment of a regional power-grid-based market. However, this strategy has been subject to many barriers. In discussing this proposal in detail, this paper focuses on national interest, policy-making and institutional issues. It is argued that if regional cooperation is to be viable in the GMS, partner nations should work towards improving international relations, adopting a flexible approach to energy policy making and energy sector reform, and balancing the basic needs of local people for energy consumption and power market issues. Mitigating the social and environmental impacts of energy projects and establishing an effective regional energy agency are also great challenges to the regional cooperation.