We argue in this paper that explaining policy innovation within health systems requires paying attention to a specific type of policy-maker, characterised here as “medical entrepreneurs” with analogy to “policy entrepreneurs,” a notion often displayed in larger heuristic frameworks of policy change for descriptive purposes, with only little theoretical elaboration. This paper provides a tentative theoretical framework to characterise medical entrepreneurs. The framework is then probed empirically through case studies of health system reform and health policy change in France.