Regional-scale hydrologic and mechanical properties, including the presence of fracture zones, were calibrated using laboratory measurements and field data. Our initial results suggest that, in general, long-term (~100 years or more) sequestration in deep brine reservoirs is possible, if guided by robust rock mechanical and hydrologic data. However, specific processes must be addressed to characterize and minimize risks. In addition to CO2 migration from target sequestration reservoirs into other reservoirs or to the land surface, another environmental issue is displacement of brines into freshwater aquifers. We evaluated the potential for such unintended aquifer contamination by displacement of brines out of adjacent sealing layers such as marine shales. Results suggest that sustained injection of CO2 may incur significant brine displacement out of adjacent sealing layers, depending on the injection history, initial brine composition, and hydrologic properties of both reservoirs and seals. Model simulations also suggest that as injection can induce abnormally high fluid pressures, or overpressures. Results indicate that injection-induced overpressures may migrate, and effective stresses may follow this migration under some conditions, as will associated rock strain. Such “strain migration” may lead to induced or reactivated fractures or faults, but can be controlled through reservoir engineering.