The expectations and challenges discussed in this chapter offer insights as to why the work of institutional review boards is so important and why persons who serve in academic medicine can contribute significantly to that work. Such persons can encourage forthright discussions of the scientific value of research as well as the needs, values, expectations, and vulnerabilities that participants may bring to the research enterprise. Such discussions in turn support the sustenance of an ethically attuned research environment, one that meets both the letter and the spirit of the regulatory guidance for protecting human subjects.