Deep-sea chemosynthetic communities may be particularly vulnerable to large climatic changes that affect ocean temperatures and circulation patterns. Chemosynthetic animals occupy narrow redox zones, mostly at hydrothermal vents, hydrocarbon seeps, or sites of organic deposition where subsurface fluids laden with reduced gases (e.g., sulfides, methane, hydrogen) meet oxygenated seawater. Dependence on chemolithoautotrophic bacteria as primary producers renders these communities susceptible to climatic changes that alter the breadth of the oxic/anoxic interface. The fossil record reveals major transitions of chemosynthetic faunas during the middle to late Mesozoic, failing to support prior hypotheses that these environments harbor an extraordinary number of ancient relics and living fossils. The molecular phylogenetic analyses summarized herein support Cenozoic (<65 Myr old) radiations for most of the dominant invertebrate taxa now occupying these habitats. Although stem ancestors for many of the mollusks, annelids and crustaceans found at vents and seeps survived the Cretaceous/Tertiary (K/T) extinction event, their contemporary crown taxa radiated mostly after the Paleocene/Eocene thermal maximum (PETM), which led to a widespread anoxic/dysoxic event in the world’s deep-ocean basins. Perhaps these findings provide a window for viewing the future of our oceans on a warming planet.