An evaluation of hydrogeologic, geochemical, engineering, monitoring, cost, and public perception issues related to CO2 sequestration in saline reservoirs is underway at Battelle with funding from the U.S. Department of Energy's National Energy Technology Laboratory. Mt. Simon Sandstone, a regionally extensive deep formation in the Midwestern United States, is being evaluated as a potential host reservoir for long-term sequestration of CO2. Regional-scale sequestration capacity estimates show that there is enormous potential storage capacity in this formation. The regional estimates however, do not account for local uncertainties due to variation in parameters such as thickness, depth, porosity, permeability, injectivity, structural features, and the cost issues. Site-specific hydrogeologic constraints on CO2 disposal were evaluated using multiphase simulation models and data from active subsurface waste disposal facilities. The simulations show the role of hydrogeologic parameters on large-scale CO2 sequestration in the deep saline formations. The injectivity is controlled by formation permeability, thickness, injection pressure, depth, and multiphase fluid flow. The simulations also calculate the mass of CO2 dissolved in the brine over time. The dissolved CO2 becomes available for geochemical reactions and possible permanent sequestration in solid phase. Finally, the selection the sequestration sites in the region is also affected by the presence of geologic faults in the vicinity, that could be activated by excessive injection pressure.