Over the last several decades, a growing group of environmental and medical historians have argued that engagement with the materiality of disease is critical to eroding the false boundaries between environment and health, and especially to the historical study of major epidemics and pandemics. This article evaluates the ways in which environmental and medical historians have engaged materiality when thinking through questions of infectious disease. It argues that far from eschewing cultural constructions of disease and analysis of medical systems, these works demonstrate that engagement with materiality in the study of disease articulates the stakes of medical regimes and practices of healing, and renders legible the multiple scales at which epidemics occur. Addressing key controversies in the use of sources, it provides examples of works that incorporate material objects, biological ideas and actors, and non-humans without falling prey to the extremes of "biological determinism" or "constructivism." It argues that commonalities in the methods employed by these works - utilization of scientific frameworks and data, multispecies analysis, attention to scale, and spatial thinking - reveal unseen and untold aspects of past pandemics. It concludes with a brief example of how these frameworks come together in practice through a case study on the history of enteric fever in Dublin, Ireland.