There are increasing expectations about the potential of medical research to produce clinically significant benefits. And the increasing public demand to participate in clinical research reflects expectations that individuals can directly benefit from research participation. At the same time, there is growing concern about the adequacy of the system of institutional review boards (IRBs) to protect the rights and welfare of human subjects. We contacted 58 IRBs based on criteria related to a larger project on informed consent in gene transfer research. The chief aim of the interviews was to determine how IRBs assess benefits in general, with more specific questions about experiences with benefit assessments in gene transfer trials as compared with other early phase research and with all clinical research. Assessment and discussion of potential benefits in clinical research is, however, underdeveloped. Addressing benefit issues and providing reliable standards and common tools for assessment is particularly timely; it will be increasingly important in the future as greater numbers of patients are enrolled in clinical trials.