This article focuses on the evolution of cooperation and mutual perceptions of two neighboring states: Romania and the Republic of Moldova. It underlines regional development and the way in which entrepreneurship, cooperation and development, take place at the border of the two states. The article's main objectives are the description of the strategies and priorities defined by the action of people engaged in regional development and entrepreneurship at the border level, the description of motivations, positive effects and problems in this process, the impact of the EU and national policies on these processes.. Data has been collected, analyzed and interpreted, starting with European, national and regional documents, regarding regional development and cross-border entrepreneurship, from political declarations of the representatives of the two countries, to basic interviews with local and regional stakeholders, with representatives of civil organizations, and small and medium enterprises who are involved in cross-border cooperation projects at the Romanian-Moldavian border as well. The main conclusions emphasize the importance of European and national politics and financing for the evolution of cooperation, for regional development and for cross-border partnership. Implications for future research and practice are discussed.