Studies involving populations considered ‘vulnerable’, ‘at-risk’, and/or ‘marginalized’, require increased sensitivity to a host of issues particularly the balance of potential risks and benefits of participation. Although subject to interpretation, these are also the core principles Institutional Research Boards (IRB) use to guide the ethics’ reviews of proposed studies. In fulfilling this function, IRBs have tremendous power including the power to determine which studies may be implemented and which populations may be studied. It is therefore critically important that the research community be familiar with the various understandings of ‘vulnerability’, ‘risk’ ‘harm’ and ‘benefit’, and works towards the development of a common understanding of these concepts in research practice. In this paper we trace the historical development of these principles and illustrate some associated problems of interpretation by referencing a recent study of past trauma in the lives of pregnant women.