A Practice Note summarizing legal, regulatory, and compliance issues that arise when an academic medical center (AMC), hospital, or research institution engages in clinical research. This Note covers scientific misconduct, human subject protection, the Common Rule, research conflicts of interest, and informed consent. It discusses enforcement of regulatory requirements by various agencies including the Department of Health and Human Services (HHS), Office of Inspector General (OIG), the Office of Human Research Protections (OHRP), the Office of Research Integrity (ORI), and the Food and Drug Administration (FDA). This Note explains the ethical and regulatory responsibilities of a research institution, its Institutional Review Board (IRB), and the investigators who conduct clinical research. This Note is based on federal law with alerts about when state or commercial payor rules may also apply.