The development of post-Cold War international relations, which resulted in the re-dimensioning of the geostrategic interests of the great powers within the modern geopolitical space, determined new structural transformations of the regional geopolitical architecture in the South-East Europe. The geopolitical position of a small state like the Republic of Moldova, due to its importance for achieving the geostrategic interests of the great powers, is more relevant for ensuring its security than its geographic dimension. The advantages and the risks for the national security of the Republic of Moldova, following the reconfiguration of the regional geopolitical conjuncture, means both opportunity to diminish the challenges for the national security that can be strengthened by applying the Euro-Atlantic oriented integrationist mechanisms and probability to preserve the buffer-state status between the North-Atlantic Alliance /the European Union and the Russian Federation by keeping the permanent neutrality status, which is disregarded by Russia that keeps its military troops and munitions in the eastern districts (rayons) of the Republic of Moldova, which will lead to ceasing the cooperation between the Republic of Moldova and the North-Atlantic Alliance / the European Union in the defense and security areas.