Central and Eastern Europe is relatively one of the youngest regions in the world in the foreign policy strategic planning of the United States. Despite having established formal diplomatic relations with countries of this region many decades or in some cases a century ago, the nature of the relations between the U.S. and them was largely defined in the new post-Cold war era. Over the last thirty-five years the international relations in this region went from a highly structured logic of bipolar confrontation between the United States-led Western block and the Soviet-led Eastern block to a more complex set of relations within the framework of the European Union, NATO, and outside these organizations. Such qualitative transformation of relations in the region -from the Cold war, to a period of peaceful cooperation, and then again to a new confrontation between the U.S., China and Russia raises a serious research question -how the United States has been defining and building up their relations with the vast number of very different countries in the new international relations contexts. The paper will try to formulate the functional value of the relations with regional counties for the strategic imperatives of the United States. In order to determine that the author will analyze the evolution of diplomatic and political relations, investments and trade dynamics, military cooperation and strategic significance of those relations for American regional security interests. This research of the U.S. foreign policy practices towards the Central and Eastern Europe will try to formulate what are the main factors that served as a driving force of the development of those relations, and to understand the scale of how those policies are dependent on the U.S. strategic imperatives towards Russia, China, or major European allies.