Despite its enormous cost, large-scale carbon capture and storage (CCS) is considered a viable strategy for significantly reducing CO2 emissions associated with coal-based electrical power generation and other industrial sources of CO2 [Intergovernmental Panel on Climate Change (2005) IPCC Special Report on Carbon Dioxide Capture and Storage. Prepared by Working Group III of the Intergovernmental Panel on Climate Change, eds Metz B, et al. (Cambridge Univ Press, Cambridge, UK); Szulczewski ML, et al. (2012) Proc Natl Acad Sci USA 109:5185-5189]. We argue here that there is a high probability that earthquakes will be triggered by injection of large volumes of CO2 into the brittle rocks commonly found in continental interiors. Because even small- to moderate-sized earthquakes threaten the seal integrity of CO2 repositories, in this context, large-scale CCS is a risky, and likely unsuccessful, strategy for significantly reducing greenhouse gas emissions.