Environmental historians are not sufficiently aware of the extent to which mid twentieth-century thinkers turned to medical geography—originally a nineteenth-century area of study—in order to think through ideas of ecology, environment, and historical reasoning. This article outlines how the French–Croatian Mirko D. Grmek, a major thinker of his generation in the history of medicine, used those ideas in his studies of historical epidemiology. During the 1960s, Grmek attempted to provide, in the context of the Annales School’s research program under the (...) leadership of Fernand Braudel, a new theoretical framework for a world history of disease. Its development was inspired by several sources, most notably the French–American Jacques M. May, who was then pioneering an opening up of medical geography and movement towards the concept of disease ecology. The cornerstone of Grmek’s “synthetic approach” to the field was the notion of “pathocenosis”. The diverse uses of this notion in the course of time—from his early agenda focused on a longue durée history of diseases in Western Antiquity to his last, relating to the new epidemiological threat of emerging infectious diseases, specifically HIV/aids—enables us firstly, to note how concepts of ecology sat uneasily alongside those of medical geography; secondly, to assess the reach and limits of his theoretical contribution to historical epidemiology; and thirdly, to understand better the uneven fortunes of his concept of pathocenosis at the end of the twentieth and beginning of the twenty-first centuries. (shrink)