This chapter focuses on the problems surrounding responses to good-faith whistleblowing, or reports that are made in reasonable belief that the complaint is true. A whistleblower is a person who calls attention to wrongdoing, usually from within an organization. Handling whistleblowers should be understood as a larger matter than simply responding when a report of misconduct arises. An effective response to whistleblowing requires fundamentally good habits of management, sensible internal checks and balances, and effective systems for determining facts when problems arise. Responding effectively, professionally, and responsibly in the face of the myriad challenges presented by a whistleblower boils down to a realistic set of policies implemented by sensible people. If a whistleblower discovers a fraud in a clinical trial affecting the treatment of patients, the ethical imperative to report is high – and so may be the potential costs of the action.