The aim of this article was to reflect on the challenges faced in building the Health Regions and Networks in Brazil. These reflections result from studies conducted in several health regions. The central challenges for the constitution of the Health Regions and Networks are as follows: the Care Model, Primary Health Care, Care for Users with Chronic Diseases, and Hospital Care. In order to consolidate the regions and networks the organization needs to incorporate an ethical sense: focusing on social, public and individual needs, derived from comprehensive care, human and social rights, in broad, multi-scale and inter-sectorial interactions, with the constitution of a systemic, regionalized innovation. Of prime importance is the capacity to devise which general principles are responsible for maintaining the unity(mode of care), seeking to outline the coherence of the different provision models that the system might develop according to the social needs in regional settings. Without that, users will continue to seek and create ways of accessing health services that challenge the rationale of those very services. Hospital reform is also required to integrate and reorient the hospital networks. These reflections are important for the SUS to uphold its solidarity project, expressed in the trinity of universality-comprehensiveness-equality.