Given a substantial importance of international river basins for providing almost 60% of global freshwater, accommodating around 42% of the world population, spanning 151 countries, producing roughly 54% of the global river discharge, development on international river basins is perceived as an important issue in bilateral or multilateral relationship of reparian states as developments by one reparian may affect the opportunities of developments by other ones. Hydropower development continues to be a “difficult-to-address” challenge for the regional cooperation and situation with the Mekong River and 6 riparian countries including China, Myanmar, Thailand, Lao DPR, Cambodia and Vietnam proves that. Focusing on the hydropower development problems in Mekong River Basin, regulation mechanisms for harmonization of using energy resources, analysis of confrontation between hydropower supporters and opposers, this research answers two significant questions: how hydropower influences on regional cooperation in the Mekong River Basin and why the reparian states can’t find compromise on using hydropower potential of the Mekong River. Politization of “water question” actualized problems not only regional but global security too. Only the establishment of an effective mechanism for managing the water resources of the Mekong River, which all reparian countries would support, could solve the complex hydropower development problems, but this is hampered by objective international contradictions between states, behind which national interests are hidden.