Numerous epithermal gold-silver deposits formed during the past 40 Ma are irregularly distributed across the Great Basin. These deposits formed in six major magmatic-tectonic settings that varied during the complex evolution of the continental margin of western North America: (1) slab rollback–ignimbrite flareup (~45–17 Ma), (2) slab rollback–ancestral Cascade arc (~35 Ma–present), (3) Yellowstone hotspot–bimodal (~16.7–3 Ma), (4) slab window (~16 Ma–present), (5) Basin and Range bimodal extensional (≤ 7 Ma), and (6) amagmatic extensional (≤ 5 Ma). Most large (> 1 Moz gold produced) deposits are Miocene (~20–8 Ma), low-, intermediate-, and high-sulfidation deposits in the southern part of the ancestral Cascade arc; late Miocene post-subduction, low-sulfidation deposits formed over the slab window; and lowsulfidation deposits related to early (16.7–15 Ma) Yellowstone hotspot magmatism formed along the northern Nevada rift and related fracture zones to the west. The world-class Round Mountain low-sulfidation deposit is the only large deposit in ignimbrite flareup rocks despite these rocks constituting the largest eruptive volume of Cenozoic magmas in the Great Basin. Intermediate to silicic composition lava dome complexes are the most common setting for epithermal deposits in the western Great Basin, whereas deposits formed in a wide range of settings and rock types during Yellowstone hotspot activity. With exception of the Round Mountain caldera, the dozens of calderas of the ignimbrite flareup do not host large epithermal deposits. Several young (≤ 5 Ma), “amagmatic” low-sulfidation deposits formed along Basin and Range fault zones in sedimentary rocks that lack proximal magmatic activity. The types and characteristics of epithermal gold-silver deposits in the Great Basin systematically vary with magmatic-tectonic setting and magma composition, and their distribution reflects the combined effects of tectonic setting of magma genesis; magma source, composition and eruptive style; crustal thickness and composition; presence of crustal-scale structural zones; climate; and preservation of deposits.