The South-eastern Europe Health Network (SEEHN) was established in 2001 to promote peace, reconciliation and health in south-eastern Europe and contribute to preparing the countries in the region for European Union integration. Its vision remains to achieve better health and well-being in south-eastern Europe through the collaborative efforts of SEEHN member states and partners. Since its inception, SEEHN has developed into a broad partnership for health that brings together southeastern European countries and organizations focused on improving health and well-being. The World Health Organization (WHO), SEEHN’s founding organization, has remained its most important partner, providing guidance and support to its policy and technical endeavours from 2001 until today. The most recent South-eastern European Health Ministers’ Forum, held in 2017 in Chisinau, Republic of Moldova, reflected on 15 years of regional collaboration in public health and endorsed the Chisinau Pledge, which presents the SEEHN framework for action until 2020. The Forum emphasized the complex and significant contribution of SEEHN to health and well-being, which in turn has had a positive impact on peace, stability and economic development in south-eastern Europe. The Forum highlighted the active role of SEEHN in influencing public health developments in both south-eastern Europe and in Europe as a whole, and in supporting its members in their response to international commitments. SEEHN ministers and partners agreed on the vast potential of SEEHN to deliver on the contemporary policy agenda, primarily related to the WHO European policy for health and well-being Health 2020 and the United Nations 2030 Agenda for Sustainable Development. This document has multiple goals: to reflect on SEEHN’s developments as a source of experience and knowledge, and on their potential to meet the demands of the contemporary context of health and well-being; to inform on SEEHN governance structures that are able to support future collaborative efforts for health and well-being in south-eastern Europe; to share examples of SEEHN’s success in leading and influencing positive health developments in south-eastern Europe; to set out a clear model for future collaboration with WHO and other partners; and to emphasize the exemplary role of the WHO Regional Office for Europe as an enabler and supporter of influential alliances for better health and well-being in the European Region.