This essay describes efforts by the University of Iowa administration and Human Subjects Office to adapt review procedures and interpret federal regulations in ways that were appropriate to the distinctive methodologies of social science and humanistic research, including applied research. Two moments of significant change in those procedures are described and several recommendations are offered for addressing the difficulties institutional review boards and applied researchers encounter when they interact: ask questions and be prepared to respond to them, in person when necessary; be reasonable and accountable and assume the other side is too; recognize that human subjects protection is complicated and that real risks are posed by procedures sometimes assumed to be risk-free by nature. The importance of an adequately funded, well-trained staff is emphasized as the precursor to all of those measures.