Carbon capture and sequestration (CCS) has the potential to enable deep reductions in global carbon dioxide (CO2) emissions, however this promise can only be fulfilled with large-scale deployment. For this to happen, CCS must be successfully embedded into a larger legal and regulatory context, and any potential risks must be effectively managed. We developed a list of outstanding research and technical questions driven by the demands of the regulatory and legal systems for the geologic sequestration (GS) component of CCS. We then looked at case studies that bound uncertainty within two of the research themes that emerge. These case studies, on surface leakage from abandoned wells and groundwater quality impacts from metals mobilization, illustrate how research can inform decision makers on issues of policy, regulatory need, and legal considerations. A central challenge is to ensure that the research program supports development of general regulatory and legal frameworks, and also the development of geological, geophysical, geochemical, and modeling methods necessary for effective GS site monitoring and verification (M&V) protocols, as well as mitigation and remediation plans. If large-scale deployment of GS is to occur in a manner that adequately protects human and ecological health and does not discourage private investment, strengthening the scientific underpinnings of regulatory and legal decision-making is crucial.