CO2 geologic-sequestration (GS) via injection wells into suitable subsurface strata is a safe, cost-effective way to mitigate climate change. However, using well cements to zonally isolate CO2 for up to 1,000 years, as required for permanent reservoir storage, may be challenging. Some researchers claim that cement fails when exposed to CO2, leading to potential leakage to the atmosphere or into underground structures that may contain drinking water. Other investigators show cement samples from 30 to 50 year-old wells that have maintained sealing integrity and prevented CO2 leakage, even though some degree of carbonation was found. This paper presents likely reasons for this disparity between research lab test results and actual well performance data, along with best practices to provide efficient cement-based zonal isolation of CO2 storage zones. Also discussed are recent laboratory results from testing cement samples surrounded by formation material treated at two different downhole conditions. In one case, the cement specimens were treated with a 40% humid CO2 at 140°F and 2,000 psi whereas in the second case they were treated with saturated CO2 in water at 200°F and 2,000 psi for various time intervals. Results show that samples of carefully designed cement systems had a mild carbonation without any sign of loss of mechanical or sealing integrity which could lead to zonal isolation failure. A newly-applied laboratory testing method used for decades for other purposes is proposed to determine CO2 sealing performance by cement in a relatively short time period compared to previous methods. In summary, this paper discusses a comprehensive approach that may be taken to help ensure long-term, effective CO2 zonal isolation in new wells, in existing wells (via remedial solutions), and in wells to be plugged and abandoned.