Carbon dioxide (CO2) sequestration in geological formations is the most direct carbon management strategy for reducing anthropogenic CO2 emissions into the atmosphere and will likely be needed for continuation of the global fossil-fuel–based economy. Storage of CO2 into depleted oil reservoirs may prove to be both cost effective and environmentally safe. However, injection of CO2 into oil reservoirs is a complex issue, spanning a wide range of scientific, technological, economic, safety, and regulatory issues. Detailed studies about the long-term impact of CO2 on the host reservoir are necessary before this technology can be deployed. This article provides an overview of a U.S. Department of Energy–sponsored project that examines CO2 sequestration in a depleted oil reservoir. The main objectives of the project are (1) to characterize the oil reservoir and its sequestration capacity; (2) to better understand CO2 sequestration-related processes; and (3) to predict and monitor the migration and ultimate fate of CO2 after injection into a depleted sandstone oil reservoir. The project is focused around a field test that involved the injection of approximately 2090 tons (2.09 million kg) of CO2 into a depleted sandstone reservoir at the West Pearl Queen field in southeastern New Mexico. Geophysical monitoring surveys, laboratory experiments, and numerical simulations were performed in support of the field experiment. Results show that the response of the West Pearl Queen reservoir during the field experiment was significantly different than predicted response based on the preinjection characterization data. Furthermore, results from a 19-month bench-scale experiments of CO2 interaction with the Queen sand were not able to be fully reproduced using the latest numerical modeling algorithms, suggesting that the current models are not capturing important geochemical interactions.