All studies involving human subjects must be reviewed and approved by an Internal Review Board (IRB). This board consists of both professional and non-professional (lay) members, and its mission is to reasonably insure that subjects in research are adequately informed about the procedures that they will undergo and that they are protected from harm. In order for successful human stress research to proceed, an investigator needs not only to understand what constitutes ethical research, but also how to convey to the IRB that best practices will be followed in the conduct of the research and that any risks to subjects are minimized. Furthermore, if there are risks to subjects, these must be explained plainly and carefully to the subjects in a consent form prior to their participation, so that the subjects can make an informed decision as to whether or not they want to proceed. Finally, if there are risks, it must be made clear that they are substantially outweighed by the potential benefits to the subject or society. In fact, it is not possible to obtain federal grant money in the USA to study stress or allostatic processes in humans without documenting the protection of human subjects and IRB approval.

Researchers often view the entire process of assembling and submitting human subjects review forms as an onerous and difficult task. Perhaps the single major complaint (or frustration) that is voiced by researchers is that they do not understand what the IRB wants.