In the wake of the rapid development of medical research over the past 50 years, investigators, clinicians, and ethicists have raised numerous concerns about the ethical conduct of research. Perhaps the single most important protective mechanism to emerge from the fray has been the requirement of informed consent. Certainly it has the longest history. However, even though informed consent has become the most widely recognized mechanism of protecting human subjects in research, there are limits to what the informed consent process can accomplish. Another, and more far-reaching, way to protect human subjects involved in research is to ensure that the study design is as consistent as possible with patients' preferences and goals. That is, pain investigators have a significant opportunity to improve the ethical rigor of their work by designing a study that offers a subject what is a reasonable balance of risks and benefits. This article suggests some specific ways in which investigators may design research that is more consistent with patient preferences. We describe several aspects of the ethical design of clinical pain research that appear to be important to patients, including the potential benefits for subjects, the benefits for future patients, the risks and burdens of research participation, and the voluntariness of a subject's choice whether to enroll. We conclude by discussing ways in which the ethical design of research might make the informed consent process more robust.