Innovations in the field of radiology have been and continue to be possible through research that includes patients or healthy volunteers, or both, as research subjects. This article describes the principles that guide the ethical conduct of research as well as the procedures by which those principles are implemented, with a focus on how the principles are relevant to human research in radiology. Furthermore, we describe particular ethical challenges that radiology researchers are likely to confront. These include distinguishing research endeavors from innovative treatment, determining the acceptability of randomization and placebos, compensating for the "therapeutic misconception" of research subjects, and deciding when to disclose test results and incidental findings from research to subjects. We offer suggestions for anticipating and resolving such issues.