Descriptive characteristics such as banding, ore and alteration mineralogy, and a relation to volcanism allow the grouping of epithermal deposits into a general class. However, the characteristics in common do not explain why some districts are economically more valuable than others. Epithermal bonanza ores form in compartmentalized networks of banded veins (i.e., discrete ore bodies) within spatially more extensive networks of banded veins. In the western Great Basin, we have found that the economic productivity of a district is linked to the details of how the district-scale system of faults that localize hydrothermal activity evolved to make compartmentalized flow and, during the Late Miocene, how regional tectonic evolution affected the compartmentalization of fluid flow. The economically important Comstock Lode, Tonopah, and Goldfield, Nevada, districts were localized in strike-slip extensional stepovers during periods of relative regional tectonic stability. Despite the evolution of these stepovers in structurally distinct patterns, the key similarity is that each resulted in compartmentalized fracture-controlled flow networks where bonanza ore is found. In the similar age, but economically less valuable, Camp Douglas, Nevada, district, the partitioning of strain led to the dispersal of fluid flow and not compartmentalization. During the course of hydrothermal activity in the Aurora, Nevada, district, basin-range extension dominated near-surface strain accommodation thereby changing the shallow permeability structure of the fracture-controlled flow system. Whereas pre-basin-range fluid flow lacked significant compartmentalization of flow due to high rates of extension, after the onset of basin-range extension the sense of motion of many faults changed, compartmentalization resulted, and high-grade ore was deposited. In summary, the key feature of districts with high economic value is the coupling of deformation and fluid flow to compartmentalize fluid flow and affect heat and chemical transport in a manner favorable to ore deposition.