Diplomatic relations between the Republic of Moldova and United States were established in 1992. Over the years, the two countries have developed the main directions of cooperation in various spheres of public life. In this article, the authors reveal the impact of the internal factors on the relationship between the Republic of Moldova and the U.S. The first section is devoted to the analysis of government programs interaction between the United States and the Republic of Moldova in various areas. The second section analyzes the role of political parties, NGO and media in the interstate cooperation between the Republic of Moldova and the U.S. The United States has always been and remains a consistent supporter of economic and democratic reforms in our country. Moldova is often presented as a model of the successful implementation of political and economic reform for other countries in the region. Nevertheless, there is still much to be done in order to solve internal problems and to realize the great potential for bilateral cooperation between United States of America and the Republic of Moldova.