Although the importance of including vulnerable populations in medical research is widely accepted, identifying how to achieve such inclusion remains a challenge. Ensuring that the language of informed consent is comprehensible to this group is no less of a challenge. Although a variety of interventions show promise for increasing the comprehensibility of informed consent and increasing a climate of exchange, consensus is lacking on which interventions should be used in which situations and current regulations provide little guidance. We argue that (...) the notion of individual autonomy — a foundational principle of informed consent — may be too narrow for some vulnerable populations by virtue of its failure to acknowledge their unique histories and current circumstances. It has a different meaning for members of structured groups like American Indians than for unstructured groups, such as African Americans, whose complicated histories foster group identity. Ensuring broad participation in research and selecting appropriate methods for obtaining informed consent — namely, methods aligned with the source of vulnerability and level of risk — require new ways of thinking that might produce guidelines for matching informed consent models and processes with subpopulations. (shrink)