AbstractIntroductionImproving the U.S. healthcare system and health outcomes is one of the most pressing public health challenges of our time. Previously described Collaborative Learning Health Systems (CLHSs) are a promising approach to outcomes improvement. In order to fully realize this promise, a deeper understanding of this phenomenon is necessary.MethodsWe drew on our experience over the past decade with CLHSs as well as qualitative literature review to answer three questions: What kind of phenomena are CLHSs? and what is an appropriate scientific approach? How might we frame CLHSs conceptually? What are potential mechanisms of action?ResultsCLHSs are complex adaptive systems in which all stakeholders are able to collaborate, at scale, to create and share resources to satisfy a variety of needs. This is accomplished by providing infrastructure and services that enable stakeholders to act on their inherent motivations. This framing has implications for both research and practice.ConclusionArticulating this framework and potential mechanisms of action should facilitate research to test and refine hypotheses as well as guide practice to develop and optimize this promising approach to improving healthcare systems.