Deep saline aquifers have received much attention as storage sites of CO2 due to their large storage capacity. However, many issues like CO2 leakage, low solubility of CO2 in brine, contamination of groundwater with CO2, injectivity impairment, corrosion in the pipeline, salt precipitation, and pore plugging are still unresolved. When supercritical CO2 is injected into the saline aquifer, its lower density causes it to migrate to the aquifer�s top, leaving the lower portion of the aquifer unswept. At the interface between free CO2 and brine, part of the CO2 slowly dissolves in the brine, developing a CO2 saturated interface with brine on top of the free brine. The density difference between saturated and free brine triggers a slow density-driven convection process within the aquifer. Researchers have extensively investigated these challenges associated with CO2 storage in saline aquifers and have explored various techniques to improve storage security. These techniques include injection of water-based fluid, brine, surfactants, polymer, and nanoparticles on or with CO2. Despite the reported success stories of these techniques, some limitations stand in the way of full-scale deployment. These include the cost of injectants, toxicity, adsorption, and pore plugging. Currently, there is a scarcity of comprehensive reviews that thoroughly analyze the methods utilized for CO2 storage in saline aquifers. Hence, the primary objective of this Review is to highlight the issues that have been encountered during the storage of CO2 in saline aquifers and to provide an overview of the benefits and challenges associated with the methods employed thus far. In addition, carbon capture and storage (CCS) projects face further hurdles due to corrosion within the pore space, leakage through injection wells, high cost of storage projects, uncertainty in the evaluation of storage capacity, and inaccurate interpretation of data. The study suggests the necessity for thorough research to address and overcome these issues. © 2023 American Chemical Society.