In order to achieve a learning health care system in which quality and effectiveness of health care are improved as costs are lowered, leveraging electronic health record data for purposes beyond treatment and payment will need to become easier and more widespread. This paper explores the current legal and policy challenges associated with secondary use of electronic clinical data, including those inherently relying on Institutional Review Board (IRB) review, and discusses a number of strategies that early health IT-adopters have employed to address them. The paper closes by noting potential changes to federal research rules that could ease restrictions on research in the future and by raising one additional policy challenge – support for health services research infrastructure – that, if unresolved, could create obstacles to further progress.