The communicable disease threats and changes that began emerging in south-east Europe in the early 1990s - after a decade of war and while political and health systems region-wide were undergoing dramatic changes - demanded a novel approach to infectious disease surveillance. Specifically, they called for an approach that was focused on cross-border collaboration and aligned with European Union standards and requirements. Thus, the Southeastern European Health Network (SEEHN) was established in 2001 as a cooperative effort among the governments of Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Moldova, Montenegro, Romania, Serbia, and the former Yugoslav Republic of Macedonia. In 2002, SEEHN initiated a communicable diseases project aimed at strengthening both national and regional surveillance systems with a focus on cross-border collaboration. Over time, SEEHN has nurtured growth of a regional fabric of SEE experts in communicable diseases surveillance and response who are able to discuss emerging issues and best practices at any time and without being constrained by the rigidity of traditional or existing systems. Main achievements to date include joint preparation of influenza pandemic preparedness plans at both national and regional levels and the introduction of molecular techniques into influenza surveillance laboratories region-wide. Here, we describe the history of the SEEHN communicable disease project; major activities and accomplishments; and future sustainability of the regional infectious disease surveillance network that has emerged and grown over the past decade.