Aim: Regional collaboration has continuously contributed to the development of public health in the South Eastern Europe (SEE) region since 2000 when the Public Health Collaboration in SEE (PH-SEE) was initiated. This article looks into two frameworks for regional collaboration in the area of public health: a framework developed in 2004 by a network of public health professionals and academics, and another one developed by the SEE Health Network as integral part of the SEE 2020 strategy on Jobs and Prosperity in a European Perspective, adopted in 2013. It compares the commonalities and differences of the two frameworks; considers what is still valid and relevant after ten years and which new features have emerged in the new strategy.Methods: A literature review was carried out and a qualitative analysis was applied for the comparison of the two frameworks.Results: Notwithstanding the time gap of nearly ten years, the commonalities between the two regional health strategies are significant. Major consistent goals include: improving equity in health; strengthening human resources for health; improving intersectoral cooperation and governance. The differences between the two regional strategies, including issues around social participation and regional health information systems, are partially due to their different development context. Cross-border policies and quality management have emerged as new or more pronounced topics in the SEE 2020 strategy’s health dimension. Conclusions: Many aspects addressed in the 2004 framework are pertinent with regard to the SEE 2020 health dimension and remain relevant in the current context. The integration of health as part of the economic SEE 2020 strategy reflects a significant paradigm shift and important step forward for public health.